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

Abstract:

: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.

journal_name

Oncogene

journal_title

Oncogene

authors

Chen C,Gupta P,Parashar D,Nair GG,George J,Geethadevi A,Wang W,Tsaih SW,Bradley W,Ramchandran R,Rader JS,Chaluvally-Raghavan P,Pradeep S

doi

10.1038/s41388-020-1194-7

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

2921-2933

issue

14

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-1194-7

journal_volume

39

pub_type

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