The ZNF304-integrin axis protects against anoikis in cancer

Burcu Aslan, Paloma Monroig, Ming-Chuan Hsu, Guillermo Armaiz Pena, Cristian Rodriguez-Aguayo, Vianey Gonzalez-Villasana, Rajesha Rupaimoole, Archana Sidalaghatta Nagaraja, Selanere Mangala, Hee-Dong Han, Erkan Yuca, Sherry Y. Wu, Cristina Ivan, Tyler J. Moss, Prahlad T. Ram, Huamin Wang, Alexandra Gol-Chambers, Ozgur Ozkayar, Pinar Kanlikilicer, Enrique Fuentes-Mattei, Nermin Kahraman, Sunila Pradeep, Bulent Ozpolat, Susan Tucker, Mien-Chie Hung, Keith Baggerly, Geoffrey Bartholomeusz, George Calin, Anil K. Sood and Gabriel Lopez-Berestein ()
Additional contact information
Burcu Aslan: University of Texas MD Anderson Cancer Center
Paloma Monroig: University of Texas MD Anderson Cancer Center
Ming-Chuan Hsu: University of Texas MD Anderson Cancer Center
Guillermo Armaiz Pena: University of Texas MD Anderson Cancer Center
Cristian Rodriguez-Aguayo: University of Texas MD Anderson Cancer Center
Vianey Gonzalez-Villasana: University of Texas MD Anderson Cancer Center
Rajesha Rupaimoole: Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
Archana Sidalaghatta Nagaraja: Graduate School of Biomedical Sciences, University of Texas MD Anderson Cancer Center
Selanere Mangala: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
Hee-Dong Han: School of Medicine, Konkuk University
Erkan Yuca: University of Texas MD Anderson Cancer Center
Sherry Y. Wu: University of Texas MD Anderson Cancer Center
Cristina Ivan: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
Tyler J. Moss: University of Texas MD Anderson Cancer Center
Prahlad T. Ram: University of Texas MD Anderson Cancer Center
Huamin Wang: University of Texas MD Anderson Cancer Center
Alexandra Gol-Chambers: University of Texas MD Anderson Cancer Center
Ozgur Ozkayar: University of Texas MD Anderson Cancer Center
Pinar Kanlikilicer: University of Texas MD Anderson Cancer Center
Enrique Fuentes-Mattei: University of Texas MD Anderson Cancer Center
Nermin Kahraman: University of Texas MD Anderson Cancer Center
Sunila Pradeep: University of Texas MD Anderson Cancer Center
Bulent Ozpolat: University of Texas MD Anderson Cancer Center
Susan Tucker: University of Texas MD Anderson Cancer Center
Mien-Chie Hung: University of Texas MD Anderson Cancer Center
Keith Baggerly: Hacettepe University School of Medicine
Geoffrey Bartholomeusz: University of Texas MD Anderson Cancer Center
George Calin: University of Texas MD Anderson Cancer Center
Anil K. Sood: Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center
Gabriel Lopez-Berestein: University of Texas MD Anderson Cancer Center

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8351

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