Cell Death and Survival Relocation of CLIC1 Promotes Tumor Cell Invasion and Colonization of Fibrin

Abstract

Chloride intracellular channel 1 (CLIC1) has been shown to be upregulated in various malignancies but its exact function remains unclear. Here, it is revealed that CLIC1 is critical for the stability of invadopodia in endothelial and tumor cells embedded in a 3-dimensional (3D) matrix of fibrin. Invadopodia stability was associated with the capacity of CLIC1 to induce stress fiber and fibronectin matrix formation following its b3 integrin (ITGB3)-mediated recruitment into invadopodia. This pathway, in turn, was relevant for fibrin colonization as well as slug (SNAI2) expression and correlated with a significant role of CLIC1 in metastasis in vivo. Mechanistically, a reduction of myosin light chain kinase (MYLK) in CLIC1-depleted as well as b3 integrin-depleted cells suggests an important role of CLIC1 for integrin-mediated actomyosin dynamics in cells embedded in fibrin. Overall, these results indicate that CLIC1 is an important contributor to tumor invasion, metastasis, and angiogenesis. Implications: This study uncovers an important new function of CLIC1 in the regulation of cell–extracellular matrix interactions and ability of tumor cells to metastasize to distant organs. Mol Cancer Res; 13(2); 273–80. 2014 AACR.

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Cite this paper

@inproceedings{Gurski2015CellDA, title={Cell Death and Survival Relocation of CLIC1 Promotes Tumor Cell Invasion and Colonization of Fibrin}, author={Lisa A. Gurski and Lynn M. Knowles and Per H. Basse and Jodi Maranchie and Simon C.Watkins and Jan Pilch}, year={2015} }