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

Cell Communication and Signaling

Review

Juliane von der Ohe¹  Ralf Hass¹  Catharina Melzer¹  Hendrik Lehnert²  Hendrik Ungefroren³ 

[1] Biochemistry and Tumor Biology Lab, Department of Obstetrics and Gynecology, Hannover Medical School, Hannover, Germany;Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany;First Department of Medicine, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany;Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany;First Department of Medicine, University Hospital Schleswig-Holstein (UKSH), Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany;Department of General and Thoracic Surgery, UKSH, Campus Kiel, Kiel, Germany;

关键词: Breast cancer;    Pancreas cancer;    Tumor cell signaling;    Tumor microenvironment;    TGF-β;    Rac1;    Metastasis;   

DOI  :  10.1186/s12964-017-0175-0

 received in 2017-03-20, accepted in 2017-05-08,  发布年份 2017

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s). 2017