The ZNF304-integrin axis protects against anoikis in cancer

Creative Commons License

Aslan B., Monroig P., Hsu M., Pena G. A., Rodriguez-Aguayo C., Gonzalez-Villasana V., ...Daha Fazla

NATURE COMMUNICATIONS, cilt.6, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 6
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1038/ncomms8351
  • Dergi Adı: NATURE COMMUNICATIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.