The role of TGF-β and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma

Cell Communication and Signaling : CCS
Catharina MelzerHendrik Ungefroren

Abstract

This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data from our and other studies point to signaling crosstalk between TGF-β and RAC1 and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based on the exciting observation that RAC1b functions as an endogenous inhibitor of RAC1, we propose a model on how the relative abundance or activity of RAC1 and RAC1b in the tumor cells may determine their responses to TGF-β and, ultimately, the metastatic capacity of the tumor.

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Citations

Aug 11, 2017·Cell & Bioscience·Wei ShenZhi-Qiang Tian
Mar 18, 2020·Cancers·Larissa Kotelevets, Eric Chastre
Jan 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Binbin MaBo Zhang
Dec 4, 2019·Oncology Letters·Sandor FerenczDezso Kelemen
Sep 8, 2018·Pathology Oncology Research : POR·Li ZhangYoulin Kuang
Nov 12, 2020·International Journal of Molecular Sciences·Catharina MelzerRalf Hass
Feb 23, 2021·The EMBO Journal·Jong Ho ParkShadmehr Demehri
Mar 7, 2021·Biomolecules·Roberta MelchionnaPaola Nisticò
Apr 15, 2021·Nature Communications·Racha FayadFrédéric Luton
Jun 3, 2021·International Journal of Molecular Sciences·Norihiko SasakiToshiyuki Ishiwata

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Methods Mentioned

BETA
GTPase
GTPases
nucleotide exchange
geranylgeranylation

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