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-MatteiNermin Kahraman, Sunila Pradeep, Bulent Ozpolat, Susan Tucker, Mien Chie Hung, Keith Baggerly, Geoffrey Bartholomeusz, George Calin, Anil K. Sood, Gabriel Lopez-Berestein

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish (US)
Article number7351
JournalNature Communications
Volume6
DOIs
StatePublished - Jun 17 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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