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TGF-β1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking
- Source :
- European journal of cell biology. 95(11)
- Publication Year :
- 2016
-
Abstract
- Transforming growth factor-β1 (TGF-β1) is an important player in chronic liver diseases inducing fibrogenesis and hepatocellular carcinoma (HCC) development. TGF-β1 promotes pleiotropic modifications at the cellular and matrix microenvironment levels. TGF-β1 was described to enhance production of type I collagen and its associated cross-linking enzyme, the lysyl oxidase-like2 (LOXL2). In addition, TGF-β1 and type I collagen are potent inducers of invadosomes. Indeed, type I collagen fibers induce the formation of active linear invadosomes through the discoidin domain receptor 1 (DDR1). The goal of our study was to address the role of TGF-β1 in collagen cross-linking and its impact on the formation of linear invadosomes in liver cancer cells. We first report a significant correlation between expressions of TGF-β1, and type I collagen, LOXL2, DDR1 and MT1-MMP in human HCCs. We demonstrate that TGF-β1 promotes a Smad4-dependent up-regulation of DDR1, together with LOXL2, in cultured HCC cells. Moreover, we show that LOXL2-induced collagen cross-linking enhances linear invadosome formation. Altogether, our data demonstrate that TGF-β1 favors linear invadosome formation through the expressions of both the inducers, such as collagen and LOXL2, and the components such as DDR1 and MT1-MMP of linear invadosomes in cancer cells. Meanwhile, our data uncover a new TGF-β1-dependent regulation of DDR1 expression.
- Subjects :
- 0301 basic medicine
Histology
Carcinoma, Hepatocellular
Collagen Type I
Pathology and Forensic Medicine
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Discoidin Domain Receptor 1
Cell Line, Tumor
Humans
Neoplasm Invasiveness
DDR1
LOXL2
Chemistry
Liver Neoplasms
Cell Biology
General Medicine
HCCS
Cell biology
Neoplasm Proteins
Up-Regulation
Gene Expression Regulation, Neoplastic
030104 developmental biology
Biochemistry
030220 oncology & carcinogenesis
Cancer cell
Type I collagen
Discoidin domain
Transforming growth factor
Subjects
Details
- ISSN :
- 16181298
- Volume :
- 95
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- European journal of cell biology
- Accession number :
- edsair.doi.dedup.....d09b4d6fefc7d403a0f5acfd72557d3d