Intracellular and extracellular TGF-β signaling in cancer: some recent topics

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.

Fibroblast growth factor signals regulate transforming growth factor‐β‐induced endothelial‐to‐myofibroblast transition of tumor endothelial cells via Elk1

“…Many tumor types are characterized by a high concentration of transforming growth factor-bs (TGFbs), which are produced by cancer cells and infiltrating inflammatory cells. Previous studies have shown that TGF-b promotes epithelial-to-mesenchymal transition (EMT) of normal and transformed epithelial cells, as well as EndMT of endothelial cells (Miyazono et al, 2018;Yoshimatsu and Watabe, 2011).…”

Inhibition of TGF-β signalling in combination with nal-IRI plus 5-Fluorouracil/Leucovorin suppresses invasion and prolongs survival in pancreatic tumour mouse models

“…It suppresses tumour progression by promoting cell cycle arrest and apoptosis in early-stage of pancreatic carcinogenesis. On the other hand, it functions as a tumour promoter by activating the Smad4-independent signalling pathway, promoting cell motility, invasion, EMT, and metastasis and decreasing anti-tumour immune responses in advanced stages 30 . Thus, inhibition of TGF-β signalling in the late stages of cancer progression could be an effective strategy for treating pancreatic cancer.…”

The Role of TGFβ in Clinical Cancer Response

“…Across a variety of cancers, TGFβ plays crucial roles in EMT, tumor metastasis, angiogenesis, and treatment resistance [19]. Due to the celltype specific role of TGFβ as opposed to a cancer-specific role, understanding the pathways and modulatory factors of TGFβ are crucial to developing a broad-spectrum cancer treatment [20].…”