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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.

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CHU de Québec-Université Laval Research Center (Oncology division), Université Laval Cancer Research Center and Faculty of Medecine, Université Laval, Québec G1R 3S3, Canada
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA.
Pathobiology Graduate Program, Brown University, Providence, RI 02912, USA.
Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37212, USA


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.


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


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