ERBB3-induced furin promotes the progression and metastasis of ovarian cancer via the IGF1R/STAT3 signaling axis.

Oncogene 2020 Apr

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High-grade serous carcinoma, accounts for up to 70% of all ovarian cases. Furin, a proprotein convertase, is highly expressed in high-grade serous carcinoma of ovarian cancer patients, and its expression is even higher in tumor omentum than in normal omentum, the preferred site of ovarian cancer metastasis. The proteolytic actions of this cellular endoprotease help the maturation of several important precursors of protein substrates and its levels increase the risk of several cancer. We show that furin activates the IGF1R/STAT3 signaling axis in ovarian cancer cells. Conversely, furin knockdown downregulated IGF1R-β and p-STAT3 (Tyr705) expression. Further, silencing furin reduced tumor cell migration and invasion in vitro and tumor growth and metastasis in vivo. Collectively, our findings show that furin can be an effective therapeutic target for ovarian cancer prevention or treatment.

Citation

Changliang Chen, Prachi Gupta, Deepak Parashar, Gopakumar G Nair, Jasmine George, Anjali Geethadevi, Wei Wang, Shirng-Wern Tsaih, William Bradley, Ramani Ramchandran, Janet S Rader, Pradeep Chaluvally-Raghavan, Sunila Pradeep. ERBB3-induced furin promotes the progression and metastasis of ovarian cancer via the IGF1R/STAT3 signaling axis. Oncogene. 2020 Apr;39(14):2921-2933