Faculty Collaboration Database

ERBB3-induced furin promotes the progression and metastasis of ovarian cancer via the IGF1R/STAT3 signaling axis. Oncogene 2020 Apr;39(14):2921-2933

Date

02/08/2020

Pubmed ID

32029900

Pubmed Central ID

PMC7346970

DOI

10.1038/s41388-020-1194-7

Scopus ID

2-s2.0-85079196544 (requires institutional sign-in at Scopus site)   34 Citations

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.

Author List

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

Authors

William H. Bradley MD Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Pradeep Chaluvally-Raghavan PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Anjali Geethadevi PHD Research Scientist I in the Obstetrics and Gynecology department at Medical College of Wisconsin
Deepak Parashar PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Cell Line, Tumor
Cell Movement
Disease Progression
Down-Regulation
Female
Furin
Gene Expression Regulation, Neoplastic
Humans
Neoplasm Invasiveness
Ovarian Neoplasms
Receptor, ErbB-3
Receptor, IGF Type 1
STAT3 Transcription Factor
Signal Transduction