Intracellular and extracellular TGF-β signaling in cancer: some recent topics.
10.1007/s11684-018-0646-8
- Author:
Kohei MIYAZONO
1
;
Yoko KATSUNO
2
;
Daizo KOINUMA
2
;
Shogo EHATA
2
;
Masato MORIKAWA
2
Author Information
1. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan. miyazono@m.u-tokyo.ac.jp.
2. Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, Japan.
- Publication Type:Journal Article
- Keywords:
EMT;
GARP;
TGF-β;
immune function;
latent form;
lung cancer;
pancreatic cancer
- MeSH:
Drug Discovery;
Humans;
Lung Neoplasms;
drug therapy;
immunology;
metabolism;
Membrane Proteins;
metabolism;
Pancreatic Neoplasms;
drug therapy;
immunology;
metabolism;
Signal Transduction;
drug effects;
physiology;
T-Lymphocytes, Regulatory;
metabolism;
Transforming Growth Factor beta;
antagonists & inhibitors;
immunology;
metabolism
- From:
Frontiers of Medicine
2018;12(4):387-411
- CountryChina
- Language:English
-
Abstract:
Transforming growth factor (TGF)-β regulates a wide variety of cellular responses, including cell growth arrest, apoptosis, cell differentiation, motility, invasion, extracellular matrix production, tissue fibrosis, angiogenesis, and immune function. Although tumor-suppressive roles of TGF-β have been extensively studied and well-characterized in many cancers, especially at early stages, accumulating evidence has revealed the critical roles of TGF-β as a pro-tumorigenic factor in various types of cancer. This review will focus on recent findings regarding epithelial-mesenchymal transition (EMT) induced by TGF-β, in relation to crosstalk with some other signaling pathways, and the roles of TGF-β in lung and pancreatic cancers, in which TGF-β has been shown to be involved in cancer progression. Recent findings also strongly suggested that targeting TGF-β signaling using specific inhibitors may be useful for the treatment of some cancers. TGF-β plays a pivotal role in the differentiation and function of regulatory T cells (Tregs). TGF-β is produced as latent high molecular weight complexes, and the latent TGF-β complex expressed on the surface of Tregs contains glycoprotein A repetitions predominant (GARP, also known as leucine-rich repeat containing 32 or LRRC32). Inhibition of the TGF-β activities through regulation of the latent TGF-β complex activation will be discussed.
