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AnyGenes

Signaling Pathways title  TGFβ Signaling Pathway

Transforming growth factor β (TGFβ) is a multi-functional secreted cytokine that plays pivotal roles in embryonic development and adult tissue maintenance (1), moreover it regulates numerous biological processes including promotion of cell differentiation and proliferation, control of cell apoptosis and cell cycle, regulation of the epithelial–mesenchymal transition (EMT), angiogenesis, extracellular matrix (ECM) formation, suppression of immune response, and maintenance of genomic stability and stem cell homeostasis (2), (in blue among AnyGenes pathways).
It has been proved that TGFβ plays dual roles in tumor progression as tumor-promoter or suppressor. In an early stage, TGFβ inhibits cell proliferation and is involved in cell apoptosis. In an advanced tumor, TGFβ signaling pathway induces tumor invasion and metastasis through promoting angiogenesis, epithelial–mesenchymal transition, and immune escape (3).
TGFβ-signaling- pathways

 
Overview of the TGFβ family pathways (7)
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Signaling Pathways title  TGFβ Signaling Pathway and diseases

Abnormal TGFβ signaling pathway cause congenital defects, fibrotic diseases, immune dysregulation (4), craniofacial cleft palate syndrome, and the autosomal dominant abnormality of the Rendu–Osler–Weber syndrome; cardiovascular pathologies including atherosclerosis, hypertension and rare abnormalities of the vasculature such as aneurysms; connective tissue and bone diseases like the Marfan syndrome and osteoporosis; muscular and reproductive disorders; certain hereditary cancer syndromes and many sporadic malignancies such as brain, breast, colon, liver, lung, prostate, haematopoetic malignancies and Cholangiocarcinoma (1,5,6,8).
TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis (7).
Recent studies have revealed roles of TGFβ pathway in tumor immune evasion and poor responses to cancer immunotherapy (4).
Targeting the TGFβ pathway for cancer therapy may be considered primarily as a microenvironment-targeted strategy (7).

(1) Suriyamurthy S et al. Epigenetic Reprogramming of TGF-β Signaling in Breast Cancer. Cancers (Basel). (2019) 24;11(5).
(2) Chen J et al. Immunomodulatory TGF-β Signaling in Hepatocellular Carcinoma. Trends Mol Med. (2019).
(3) Chen Y et al. Transforming growth factor β signaling pathway: A promising therapeutic target for cancer. J Cell Physiol. (2019).
(4) Batlle E et Massagué J. Transforming Growth Factor-β Signaling in Immunity and Cancer. Immunity. (2019) 16;50(4):924-940.
(5) Pellatt AJ et al.The TGFβ-signaling pathway and colorectal cancer: associations between dysregulated genes and miRNAs. J Transl Med. (2018);16(1):191.
(6) Papoutsoglou P et al. Transforming Growth Factor-Beta (TGFβ) Signaling Pathway in Cholangiocarcinoma.Cells. (2019)23;8(9).
(7) Neuzillet C et al. Targeting the TGFβ pathway for cancer therapy. PharmacolTher. (2015);147:22-31.
(8) Bellomo C et al. Transforming growth factor β as regulator of cancer stemness and metastasis. Br J Cancer. 2016 Sep 27;115(7):761-9 
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