The ZNF304-integrin axis protects against anoikis in cancer. Nat Commun 2015 Jun 17;6:7351
Date
06/18/2015Pubmed ID
26081979Pubmed Central ID
PMC4830335DOI
10.1038/ncomms8351Scopus ID
2-s2.0-84935895247 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
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.
Author List
Aslan B, Monroig P, Hsu MC, Pena GA, Rodriguez-Aguayo C, Gonzalez-Villasana V, Rupaimoole R, Nagaraja AS, Mangala S, Han HD, Yuca E, Wu SY, Ivan C, Moss TJ, Ram PT, Wang H, Gol-Chambers A, Ozkayar O, Kanlikilicer P, Fuentes-Mattei E, Kahraman N, Pradeep S, Ozpolat B, Tucker S, Hung MC, Baggerly K, Bartholomeusz G, Calin G, Sood AK, Lopez-Berestein GAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnoikisCarcinoma
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Integrin beta Chains
Ovarian Neoplasms
Transcription Factors