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J Cell Sci. 2020 Jan 3;133(1). pii: jcs231134. doi: 10.1242/jcs.231134.

Tissue transglutaminase 2 regulates tumor cell tensional homeostasis by increasing contractility.

Author information

1
CHU de Québec-Université Laval Research Center (Oncology division), Université Laval Cancer Research Center and Faculty of Medecine, Université Laval, Québec G1R 3S3, Canada francois.bordeleau@fmed.ulaval.ca cynthia.reinhart-king@vanderbilt.edu.
2
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA.
3
Pathobiology Graduate Program, Brown University, Providence, RI 02912, USA.
4
Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
5
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA francois.bordeleau@fmed.ulaval.ca cynthia.reinhart-king@vanderbilt.edu.

Abstract

Abnormal tensional cellular homeostasis is now considered a hallmark of cancer. Despite this, the origin of this abnormality remains unclear. In this work, we investigated the role of tissue transglutaminase 2 (TG2, also known as TGM2), a protein associated with poor prognosis and increased metastatic potential, and its relationship to the EGF receptor in the regulation of the mechanical state of tumor cells. Remarkably, we observed a TG2-mediated modulation of focal adhesion composition as well as stiffness-induced FAK activation, which was linked with a distinctive increase in cell contractility, in experiments using both pharmacological and shRNA-based approaches. Additionally, the increased contractility could be reproduced in non-malignant cells upon TG2 expression. Moreover, the increased cell contractility mediated by TG2 was largely due to the loss of EGFR-mediated inhibition of cell contractility. These findings establish intracellular TG2 as a regulator of cellular tensional homeostasis and suggest the existence of signaling switches that control the contribution of growth factor receptors in determining the mechanical state of a cell.

KEYWORDS:

Cell contractility; Epithelial growth factor receptor; Focal adhesion; Matrix stiffness; Mechanotransduction; Tissue transglutaminase

PMID:
31822629
DOI:
10.1242/jcs.231134

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