TGFβ: A player on multiple fronts in the tumor microenvironment

Abstract

The physiological functions of transforming growth factor (TGF)-in cell signaling include regulation of developmental processes and cell growth. Tumor cells very often display altered regulation of the TGF signaling pathway, either by defects in TGF itself or in downstream components of the pathway. TGF can play a dual role in tumorigenesis, i.e. it can be either tumor-suppressive or tumor-promoting. TGF suppresses the growth of tumor cells; however, in advanced tumors, it is associated with induction of progression, resulting in poor prognosis for patients. The TGF negative regulation of cytotoxic cell function, together with the promotion of T-regulatory cell maturation, impairs anti-tumor responses. Recent studies have elucidated new roles for TGF signaling in the tumor microenvironment. Abrogation of proper signaling induces epithelial-to-mesenchymal transition with pro-metastatic functions, resulting in cancer progression. Thus, TGF signaling in the tumor microenvironment plays an important role in tumor initiation, progression, and metastasis by its capacity to regulate cross-talk between tumor cells and other components of the local environment.

Role of the TGFβ/PDCD4/AP-1 Signaling Pathway in Nasopharyngeal Carcinoma and Its Relationship to Prognosis

“…A previous study demonstrated that TGFβ expression in tumor cells is promoted by surrounding cells in the tumor microenvironment [28]. It has been reported that TGF-β1 was overexpressed in several cancers such as hepatocellular carcinoma and it was related to the progression of tumor cells [29, 30].…”

Transforming Growth Factor β Superfamily Signaling in Development of Colorectal Cancer

“…TGF- β regulates proliferation, differentiation, and functions of immune cells that include macrophages, dendritic cells, natural killer cells, B cells, and T cells. TGF- β also modulates innate and adaptive immunity (reviewed by Caja and Vannucci 85 ). The role of TGF- β in the regulation of T-cell maturation, proliferation, and expansion is particularly relevant to cancer progression.…”

Furin as proprotein convertase and its role in normal and pathological biological processes

“…Основная функция TGF-b в большинстве клеток и тканей связана с контролем пролиферации и дифференцировки [92][93][94][95]. В нормальных эпителиальных клетках, а также на ранних стадиях опухолевой прогрессии (в премалигнизированных или хорошо дифференцированных раковых клетках) TGF-b действует как антипролиферативный фактор, угнетая канцерогенез, инвазивные и метастатические процессы [95,96]. Однако на поздних стадиях рака он поддерживает рост опухолей и метастазирование [92][93][94][97][98][99][100][101].…”