The Znf304-Integrin Axis Protects Against Anoikis In Cancer

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Date
2015
Author
Aslan, Burcu
Monroig, Paloma
Hsu, Ming-Chuan
Pena, Guillermo Armaiz
Rodriguez-Aguayo, Cristian
Gonzalez-Villasana, Vianey
Rupaimoole, Rajesha
Nagaraja, Archana Sidalaghatta
Mangala, Selanere
Han, Hee-Dong
Yuca, Erkan
Wu, Sherry Y.
Ivan, Cristina
Moss, Tyler J.
Ram, Prahlad T.
Wang, Huamin
Gol-Chambers, Alexandra
Ozkayar, Ozgur
Kanlikilicer, Pinar
Fuentes-Mattei, Enrique
Kahraman, Nermin
Pradeep, Sunila
Ozpolat, Bulent
Tucker, Susan
Hung, Mien-Chie
Baggerly, Keith
Bartholomeusz, Geoffrey
Calin, George
Sood, Anil K.
Lopez-Berestein, Gabriel
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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 beta 1 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 beta 1 integrin, promotes cancer cell survival and protects against anoikis in OC.
URI
https://doi.org/10.1038/ncomms8351
http://hdl.handle.net/11655/17043
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