title: Role of Increased n-acetylaspartate Levels in Cancer.
abstract: BACKGROUND
  The clinical and biological effects of metabolic alterations in cancer are not fully understood.
  
  
  METHODS
  In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6-10 mice/group) settings. Data were analyzed with the Student's t test and Kaplan-Meier analysis. Statistical tests were two-sided.
  
  
  RESULTS
  Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L. The overall survival duration of patients with higher-than-median NAA levels (3.6 years) was lower than that of patients with lower-than-median NAA levels (5.1 years, P = .03). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) was associated with worse overall survival. NAT8L silencing reduced cancer cell viability (HEYA8: control siRNA 90.61% ± 2.53, NAT8L siRNA 39.43% ± 3.00, P < .001; A2780: control siRNA 90.59% ± 2.53, NAT8L siRNA 7.44% ± 1.71, P < .001) and proliferation (HEYA8: control siRNA 74.83% ± 0.92, NAT8L siRNA 55.70% ± 1.54, P < .001; A2780: control siRNA 50.17% ± 4.13, NAT8L siRNA 26.52% ± 3.70, P < .001), which was rescued by addition of NAA. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduced tumor growth statistically significantly (A2780: control siRNA 0.52 g ± 0.15, NAT8L siRNA 0.08 g ± 0.17, P < .001; HEYA8: control siRNA 0.79 g ± 0.42, NAT8L siRNA 0.24 g ± 0.18, P = .008, A375-SM: control siRNA 0.55 g ± 0.22, NAT8L siRNA 0.21 g ± 0.17 g, P = .001). NAT8L silencing downregulated the anti-apoptotic pathway, which was mediated through FOXM1.
  
  
  CONCLUSIONS
  These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target for anticancer therapy.Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3). Moreover, altered cancer metabolism elevates unique metabolic intermediates, which can promote cancer survival and progression (4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet their high demand for energy and to accumulate biomass (6-8).
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zand
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Previs
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Niki M
authors.initials: NM
authors.lastname: Zacharias
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Takashi
authors.initials: T
authors.lastname: Mitamura
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Archana Sidalaghatta
authors.initials: AS
authors.lastname: Nagaraja
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Michele
authors.initials: M
authors.lastname: Guindani
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Yang
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Joelle
authors.initials: J
authors.lastname: Baddour
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Achreja
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCullough
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Kshipra M
authors.initials: KM
authors.lastname: Gharpure
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Einav
authors.initials: E
authors.lastname: Shoshan
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Lingegowda S
authors.initials: LS
authors.lastname: Mangala
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Armaiz-Pena
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Baggerly
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Menashe Bar
authors.initials: MB
authors.lastname: Eli
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Deepak
authors.initials: D
authors.lastname: Nagrath
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX.
authors.forename: Pratip K
authors.initials: PK
authors.lastname: Bhattacharya
authors.affiliation: Departments of Gynecologic Oncology and Reproductive Medicine (BZ, RAP, RR, TM, ASN, HJD, WH, CI, SYW, KMG, SP, LSM, AMN, GAP, AKS), Cancer Systems Imaging (NMZ, CRM, PKB), Biostatistics (MG), Cancer Medicine (CVP), Center for RNA Interference and Non-Coding RNA (CI, LSM, CRA, GLB, AKS), Cancer Biology (YS, MBE, GLB, AKS), Experimental Therapeutics (CRA, GLB), Bioinformatics and Computational Biology (YW, KAB), Melanoma Medical Oncology (MAD), and Pathology (JL), University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Nanomedicine and Bioengineering, UT Health, Houston, TX (GLB, AKS); Departments of Psychology, Urology, and Obstetrics and Gynecology, the University of Iowa, Iowa City, IA (SKL); Laboratory for Systems Biology of Human Diseases (LY, JB, AA, DN), Department of Chemical and Biomolecular Engineering (LY, JB, AA, DN), and Department of Bioengineering (DN), Rice University, Houston, TX. asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D001224:Aspartic Acid; C000179:N-acetylaspartate; D000123:Acetyltransferases; C116373:NAT8 protein, human
references.citation: Science. 2010 Sep 17;329(5998):1492-9
references.pmid: 20847263
references.citation: Nature. 2009 Feb 12;457(7231):910-4
references.pmid: 19212411
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: N Engl J Med. 2008 Dec 18;359(25):2641-50
references.pmid: 19092150
references.citation: Mol Syst Biol. 2014;10:728
references.pmid: 24799285
references.citation: Brain Res. 2010 Jun 4;1335:1-13
references.pmid: 20385109
references.citation: Cell Metab. 2008 Jan;7(1):11-20
references.pmid: 18177721
references.citation: J Cheminform. 2010 Oct 18;2(1):9
references.pmid: 20955607
references.citation: Nature. 2011 Aug 18;476(7360):346-50
references.pmid: 21760589
references.citation: Science. 2013 Mar 29;339(6127):1621-5
references.pmid: 23393090
references.citation: PLoS One. 2011;6(5):e19963
references.pmid: 21625518
references.citation: J Natl Cancer Inst. 1989 Sep 20;81(18):1406-12
references.pmid: 2778827
references.citation: Neurosurgery. 2012 Aug;71(2):454-63
references.pmid: 22517254
references.citation: Nature. 2011 Jun 30;474(7353):609-15
references.pmid: 21720365
references.citation: J Biol Chem. 1954 Dec;211(2):927-39
references.pmid: 13221598
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references.pmid: 12883005
references.citation: Nature. 2013 Apr 4;496(7443):101-5
references.pmid: 23535601
references.citation: PLoS One. 2012;7(7):e40221
references.pmid: 22844400
references.citation: J Natl Cancer Inst. 2006 Nov 1;98(21):1558-70
references.pmid: 17077358
references.citation: BMC Genomics. 2012;13:282
references.pmid: 22732065
references.citation: J Natl Cancer Inst. 2008 Mar 5;100(5):359-72
references.pmid: 18314475
references.citation: Nat Med. 2006 Aug;12(8):939-44
references.pmid: 16862152
references.citation: Neuro Oncol. 2013 May;15(5):607-17
references.pmid: 23393206
references.citation: Radiol Med. 2012 Aug;117(5):780-8
references.pmid: 22095426
references.citation: Pharmacogenomics. 2008 Apr;9(4):383-97
references.pmid: 18384253
references.citation: J Biol Chem. 1957 Jan;224(1):41-5
references.pmid: 13398385
references.citation: Anal Chem. 2009 Aug 15;81(16):6656-67
references.pmid: 19624122
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20429-34
references.pmid: 19915147
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5198-208
references.pmid: 18698038
references.citation: Cell Death Dis. 2014;5:e1302
references.pmid: 24967964
references.citation: Clin Cancer Res. 2009 Nov 1;15(21):6479-83
references.pmid: 19861459
references.citation: Cancer Cell. 2010 Aug 9;18(2):185-97
references.pmid: 20708159
references.citation: Clin Cancer Res. 2010 Jul 1;16(13):3356-67
references.pmid: 20460471
references.citation: J Oncol. 2011;2011:174019
references.pmid: 21577256
references.citation: Cancer Res. 2015 Jan 15;75(2):456-71
references.pmid: 25425006
references.citation: Prog Neurobiol. 2007 Feb;81(2):89-131
references.pmid: 17275978
references.citation: Biochem J. 2010 Jan 1;425(1):127-36
references.pmid: 19807691