title: The ZNF304-integrin axis protects against anoikis in cancer.
abstract: Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates β1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 siRNA by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of β1 integrin, promotes cancer cell survival and protects against anoikis in OC.
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Aslan
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|University of Puerto Rico School of Medicine, Reparto Metropolitano 1160 Ave Americano Miranda, San Juan 00936, Puerto Rico.
authors.forename: Paloma
authors.initials: P
authors.lastname: Monroig
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|National Institute of Cancer Research, National Health Research Institutes, No: 367, Shengli Road,Tainan City 704, Taiwan (ROC).
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Hsu
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Guillermo Armaiz
authors.initials: GA
authors.lastname: Pena
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Rodriguez-Aguayo
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Vianey
authors.initials: V
authors.lastname: Gonzalez-Villasana
authors.affiliation: Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Rajesha
authors.initials: R
authors.lastname: Rupaimoole
authors.affiliation: Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Archana Sidalaghatta
authors.initials: AS
authors.lastname: Nagaraja
authors.affiliation: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Selanere
authors.initials: S
authors.lastname: Mangala
authors.affiliation: Department of Immunology, School of Medicine, Konkuk University, 268 Chungwondaero,Chungcheongbukdo 380-701, South Korea.
authors.forename: Hee-Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Erkan
authors.initials: E
authors.lastname: Yuca
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Sherry Y
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Cristina
authors.identifier: http://orcid.org/0000-0002-4848-0168
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Moss
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Prahlad T
authors.initials: PT
authors.lastname: Ram
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gol-Chambers
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Pathology, Hacettepe University School of Medicine, Ankara 06100, Turkey.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Ozkayar
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Pinar
authors.initials: P
authors.lastname: Kanlikilicer
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Fuentes-Mattei
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Nermin
authors.initials: N
authors.lastname: Kahraman
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Bulent
authors.initials: B
authors.lastname: Ozpolat
authors.affiliation: Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Tucker
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Center for Molecular Medicine and Institute of Cancer Biology, China Medical University, No.91, Xueshi Road, Taichung City 404, Taiwan (ROC).
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.affiliation: Department of Pathology, Hacettepe University School of Medicine, Ankara 06100, Turkey.
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bartholomeusz
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: George
authors.initials: G
authors.lastname: Calin
authors.affiliation: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.|Department of Cancer Biology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
mesh_terms: D023102:Anoikis; D002277:Carcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D039641:Integrin beta Chains; D014157:Transcription Factors; C457777:ZNF304 protein, human