title: Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer.
abstract: Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC). Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jun Hyoung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Sajna
authors.initials: S
authors.lastname: Vithayathil
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Institute of Clinical Medicine, National Yang-Ming University and Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan.
authors.forename: Pi-Lin
authors.initials: PL
authors.lastname: Sung
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Lacey Elizabeth
authors.initials: LE
authors.lastname: Dobrolecki
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Vasanta
authors.initials: V
authors.lastname: Putluri
authors.affiliation: Agilent Technologies, Wilmington, DE 19808, USA.
authors.forename: Vadiraja B
authors.initials: VB
authors.lastname: Bhat
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Salil Kumar
authors.initials: SK
authors.lastname: Bhowmik
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Kavisha
authors.initials: K
authors.lastname: Arora
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Danli
authors.initials: D
authors.lastname: Wu
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Efrosini
authors.initials: E
authors.lastname: Tsouko
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Maity
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Taraka R
authors.initials: TR
authors.lastname: Donti
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Brett H
authors.initials: BH
authors.lastname: Graham
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA; Genomic Medicine Program, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Frigo
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Coarfa
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Yotnda
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Nagireddy
authors.initials: N
authors.lastname: Putluri
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Sreekumar
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lewis
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: ljwong@bcm.edu.
authors.forename: Lee-Jun C
authors.initials: LC
authors.lastname: Wong
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: kaippare@bcm.edu.
authors.forename: Benny Abraham
authors.initials: BA
authors.lastname: Kaipparettu
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D016513:Mice, SCID; D008928:Mitochondria / Q000378:metabolism*; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D019061:src-Family Kinases