COL11A1 activates cancer-associated fibroblasts by modulating TGF-beta 3 through the NF-kappa B/IGFBP2 axis in ovarian cancer cells

doi:10.1038/s41388-021-01865-8

CNU IR > Pharmacy and Science > Dept. of Cosmetic Science and institute of cosmetic science > Periodical Articles > Item 310902800/34409

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/34409

Title:	COL11A1 activates cancer-associated fibroblasts by modulating TGF-beta 3 through the NF-kappa B/IGFBP2 axis in ovarian cancer cells
Authors:	Wu, Yi-Hui Huang, Yu-Fang Chang, Tzu-Hao Chen, Chien-Chin Wu, Pei-Ying Huang, Soon-Cen Chou, Cheng-Yang
Contributors:	Chi Mei Med Ctr, Dept Med Res Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Obstet & Gynecol Taipei Med Univ, Grad Inst Biomed Informat Chia Yi Christian Hosp, Dept Pathol, Ditmanson Med Fdn Chia Nan Univ Pharm & Sci, Dept Cosmet Sci Chi Mei Med Ctr, Dept Obstet & Gynecol
Keywords:	NF-KAPPA-B TGF-BETA BREAST-CANCER CARCINOMA GROWTH EXPRESSION IL-6 CHEMORESISTANCE SIGNATURE SURVIVAL
Date:	2021
Issue Date:	2023-11-11 11:50:23 (UTC+8)
Publisher:	SPRINGERNATURE
Abstract:	Ovarian cancer has a unique tumor microenvironment (TME) that enables cancer-associated fibroblasts (CAFs) to interact with cellular and matrix constituents and influence tumor development and migration into the peritoneal cavity. Collagen type XI alpha 1 (COL11A1) is overexpressed in CAFs; therefore this study examines its role during CAF activation in epithelial ovarian cancer (EOC). Coculturing human ovarian fibroblasts (HOFs) with high COL11A1-expressing EOC cells or exposure to the conditioned medium of these cells prompted the expression of COL11A1 and CAF phenotypes. Conversely, coculturing HOFs with low COL11A1-expressing EOC cells or COL11A1-knockdown abrogated COL11A1 overexpression and secretion, in addition to CAF activation. Increased p-SP1 expression attributed to COL11A1-mediated extracellular signal-regulated kinase activation (ERK) induced p65 translocation into the nucleus and augmented its binding to the insulin-like growth factor binding protein 2 (IGFBP2) promoter, ultimately inducing TGF-beta 3 activation. The CAF-cancer cell crosstalk triggered interleukin-6 release, which in turn promoted EOC cell proliferation and invasiveness. These in vitro results were confirmed by in vivo findings in a mouse model, showing that COL11A1 overexpression in EOC cells promoted tumor formation and CAF activation, which was inhibited by TGF-beta 3 antibody. Human tumors with high TGF-beta 3 levels showed elevated expression of COL11A1 and IGFBP2, which was associated with poor survival. Our findings suggest the possibility that anti-TGF-beta 3 treatment strategy may be effective in targeting CAFs in COL11A1-positive ovarian tumors.
Relation:	ONCOGENE, v.40, n.26, pp.4503-4519
Appears in Collections:	[Dept. of Cosmetic Science and institute of cosmetic science] Periodical Articles

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