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

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 met...

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Published in:Oncogene Vol. 39; no. 14; pp. 2921 - 2933
Main Authors: Chen, Changliang, Gupta, Prachi, Parashar, Deepak, Nair, Gopakumar G, George, Jasmine, Geethadevi, Anjali, Wang, Wei, Tsaih, Shirng-Wern, Bradley, William, Ramchandran, Ramani, Rader, Janet S, Chaluvally-Raghavan, Pradeep, Pradeep, Sunila
Format: Journal Article
Language:English
Published: England Nature Publishing Group 02.04.2020
Subjects:
Carcinoma, Ovarian Epithelial - metabolism
Carcinoma, Ovarian Epithelial - pathology
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement - physiology
Disease Progression
Down-Regulation - physiology
ErbB-3 protein
Female
Furin
Furin - metabolism
Gene Expression Regulation, Neoplastic
Humans
Metastases
Metastasis
Neoplasm Invasiveness - pathology
Omentum
Ovarian cancer
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Proprotein convertases
Proteolysis
Receptor, ErbB-3 - metabolism
Receptor, IGF Type 1 - metabolism
Signal Transduction - physiology
Stat3 protein
STAT3 Transcription Factor - metabolism
Therapeutic applications
Therapeutic targets
ISSN:0950-9232, 1476-5594, 1476-5594
Online Access:Get full text
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Summary: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.
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ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-020-1194-7