The ZNF304-integrin axis protects against anoikis in cancer

• Published in: Nature communications Vol. 6; no. 1; p. 7351
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.06.2015; Nature Publishing Group
• Subjects: 38; 59; 631/80/82/23; 631/80/86; 692/699/67/1059/602; 692/699/67/1517/1709; 82/1; 82/80; 96; 96/106; 96/2; 96/21; 96/31; Anoikis; Biology; Cancer; Carcinoma - metabolism; Cell Line, Tumor; Cell Movement; Cell Proliferation; Colorectal cancer; Datasets; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Genes; Genomes; Humanities and Social Sciences; Humans; Integrin beta Chains - metabolism; Kinases; Medical prognosis; Medical research; Medicine; Metastasis; multidisciplinary; Nanoparticles; Ovarian cancer; Ovarian Neoplasms - metabolism; Patients; Proteins; Science; Science (multidisciplinary); Survival; Transcription factors; Transcription Factors - metabolism; Tumors; Zinc finger proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms8351

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. Ovarian cancer is often accompanied by metastases at the time of diagnosis and has a poor survival rate. In this study, Aslan et al. identify a role for ZNF304 in ovarian cancer metastasis and show that the protein transcriptionally regulates β1 integrin, resulting in a reduction in programmed cell death.