Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy

• Published in: International immunopharmacology Vol. 89; no. Pt B; p. 107101
• Main Authors: Zhao, Haodi, Wei, Jing, Sun, Jian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2020; Elsevier BV
• Subjects: Animals; Apoptosis; Autocrine signalling; Biological activity; Cancer; Cancer therapies; Carcinoma; Cell differentiation; Cell proliferation; Growth factors; Humans; Immune cells; Immune Checkpoint Inhibitors - therapeutic use; Immune response; Immune system; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - metabolism; Paracrine signalling; Receptors, Transforming Growth Factor beta - antagonists & inhibitors; RNA, Messenger - antagonists & inhibitors; Selectivity; Senescence; Signal transduction; Signal Transduction - drug effects; Signal Transduction - immunology; Signaling; TGF-β inhibitors; TGF-β signaling; Transforming Growth Factor beta - antagonists & inhibitors; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; SMIs; TGF-βRII; JNK; SLC; LRRC32; nTregs; PI3K; mTOR; SHIP; MH; AMH; PFS; MAPKs; MM; ORRs; PKB; DAPK; TGF-β inhibitors; HCC; GDFs; EMT; TCGA; RGD; MMP; RCC; I-SMADs; CRC; GARP; VEGFs; PD-1; LLC; TCR; ICIs; PDA; Co-SMADs; PD-L1; TGF-β; CTLA-4; AON; APCs; MSI; Tumor microenvironment; BMP; OS; NSCLC; R-SMADs; TGF-β signaling; BIM; iTregs; TME; ECM; TEAE; PAC; LTBP; LAP; CTL; Immune cells; TGF-βRI
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.107101

•TGF-β has pleiotropic effects on the biological process including cancer progression through SMAD-dependent or independent signaling pathway.•TGF-β plays paradoxical roles in the tumor microenvironment: as a tumor suppressor at the early-stage; but as a tumor promoter at the late-stage.•Agents targeting TGF-β signal pathway have shown promising prospects in cancer therapy.
Transforming growth factor β (TGF- β) signaling pathway has pleiotropic effects on cell proliferation, differentiation, adhesion, senescence, and apoptosis. TGF-β can be widely produced by various immune or non-immune cells and regulate cell behaviors through autocrine and paracrine. It plays essential roles in biological processes including embryological development, immune response, and tumor progression. Few cell signalings can contribute to so many pleiotropic functions as the TGF- β signaling pathway in mammals. The significant function of TGF-β signaling in tumor progression and evasion leading it to draw great attention in scientific and clinical research. Understanding the mechanism of TGF- β signaling provides us with chances to potentiate the effectiveness and selectivity of this therapeutic method. Herein, we review the molecular and cellular mechanisms of TGF-β signaling in carcinomas and tumor microenvironment. Then, we enumerate main achievements of TGF-β blockades used or being evaluated in cancer therapy, providing us opportunities to improve therapeutical approaches in the tumor which thrive in a TGF-β-rich environment.