| Literature DB >> 26081979 |
Burcu Aslan1,2,3, Paloma Monroig1,2,4, Ming-Chuan Hsu5,6, Guillermo Armaiz Pena7, Cristian Rodriguez-Aguayo1,3, Vianey Gonzalez-Villasana1, Rajesha Rupaimoole2,7, Archana Sidalaghatta Nagaraja2,7,8, Selanere Mangala3,7, Hee-Dong Han9, Erkan Yuca10, Sherry Y Wu7, Cristina Ivan3,7, Tyler J Moss11, Prahlad T Ram11, Huamin Wang12, Alexandra Gol-Chambers1, Ozgur Ozkayar1,13, Pinar Kanlikilicer1, Enrique Fuentes-Mattei12, Nermin Kahraman1, Sunila Pradeep7, Bulent Ozpolat1, Susan Tucker14, Mien-Chie Hung5,15, Keith Baggerly13, Geoffrey Bartholomeusz1, George Calin1,3,8, Anil K Sood3,7,8, Gabriel Lopez-Berestein1,3,8.
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.Entities:
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Year: 2015 PMID： 26081979 PMCID： PMC4830335 DOI： 10.1038/ncomms8351
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919