TGF-β signaling pathway: Therapeutic targeting and potential for anti-cancer immunity.

Autor: Ali S; Cytogenetics and Molecular Biology Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, 190006, Jammu and Kashmir, India; Department of Biochemistry, Government Medical College, Srinagar, 190010, Jammu and Kashmir, India; Multidisciplinary Research Unit (MRU), Government Medical College, Srinagar, 190010, Jammu and Kashmir, India., Rehman MU; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia. Electronic address: muneebjh@gmail.com., Yatoo AM; Cytogenetics and Molecular Biology Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, 190006, Jammu and Kashmir, India., Arafah A; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia., Khan A; Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, 45142, Saudi Arabia., Rashid S; Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia., Majid S; Department of Biochemistry, Government Medical College, Srinagar, 190010, Jammu and Kashmir, India., Ali A; Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Kashmir (SKUAST-K), Shuhama Campus (Alusteng), Ganderbal, 190006, Jammu and Kashmir, India., Ali MN; Cytogenetics and Molecular Biology Laboratory, Centre of Research for Development, University of Kashmir, Srinagar, 190006, Jammu and Kashmir, India.
Jazyk: angličtina
Zdroj: European journal of pharmacology [Eur J Pharmacol] 2023 May 15; Vol. 947, pp. 175678. Date of Electronic Publication: 2023 Mar 27.
DOI: 10.1016/j.ejphar.2023.175678
Abstrakt: Transforming growth factor-β (TGFβ) is a pleiotropic secretory cytokine exhibiting both cancer-inhibitory and promoting properties. It transmits its signals via Suppressor of Mother against Decapentaplegic (SMAD) and non-SMAD pathways and regulates cell proliferation, differentiation, invasion, migration, and apoptosis. In non-cancer and early-stage cancer cells, TGFβ signaling suppresses cancer progression via inducing apoptosis, cell cycle arrest, or anti-proliferation, and promoting cell differentiation. On the other hand, TGFβ may also act as an oncogene in advanced stages of tumors, wherein it develops immune-suppressive tumor microenvironments and induces the proliferation of cancer cells, invasion, angiogenesis, tumorigenesis, and metastasis. Higher TGFβ expression leads to the instigation and development of cancer. Therefore, suppressing TGFβ signals may present a potential treatment option for inhibiting tumorigenesis and metastasis. Different inhibitory molecules, including ligand traps, anti-sense oligo-nucleotides, small molecule receptor-kinase inhibitors, small molecule inhibitors, and vaccines, have been developed and clinically trialed for blocking the TGFβ signaling pathway. These molecules are not pro-oncogenic response-specific but block all signaling effects induced by TGFβ. Nonetheless, targeting the activation of TGFβ signaling with maximized specificity and minimized toxicity can enhance the efficacy of therapeutic approaches against this signaling pathway. The molecules that are used to target TGFβ are non-cytotoxic to cancer cells but designed to curtail the over-activation of invasion and metastasis driving TGFβ signaling in stromal and cancer cells. Here, we discussed the critical role of TGFβ in tumorigenesis, and metastasis, as well as the outcome and the promising achievement of TGFβ inhibitory molecules in the treatment of cancer.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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