The Role of Twisted Gastrulation 1 (TWSG1) Gene in TGF-β Signaling Linked to Cancer: A Comprehensive Review

Kumar K S, Praveen; Narahari, Jyothi M; Narayana, Pramod; Prashant, Akila

doi:10.31557/APJCP.2025.26.4.1129

The Role of Twisted Gastrulation 1 (TWSG1) Gene in TGF-β Signaling Linked to Cancer: A Comprehensive Review

Document Type : Systematic Review and Meta-analysis

Authors

¹ Department of Medical Genetics, JSS Medical College and Hospital, JSS-AHER, Mysuru, India.

² SIG-TRRG, JSS Medical College and Hospital, JSS-AHER, Mysuru, India.

³ Department of Biochemistry, JSS Medical College and Hospital, JSS-AHER, Mysuru, India.

10.31557/APJCP.2025.26.4.1129

Abstract

Background: Transforming Growth Factor-beta (TGF-β) signaling is a crucial pathway in cancer development, affecting key processes such as cell growth, differentiation, and the spread of cancer cells. Recent research highlights the role of Twisted Gastrulation Protein Homolog 1 (TWSG1) as an important regulator of TGF-β signaling, showing both tumour-promoting and tumour-suppressing activities depending on the type of cancer and its specific context. Objective: This review provides a detailed overview of how TWSG1 influences TGF-β signaling in different cancers, including breast, colorectal, pancreatic, and lung. It also explores the potential of TWSG1 as a therapy target and as a biomarker for predicting patient outcomes. Methods: A thorough review of the current literature was conducted to understand how TWSG1 affects TGF-β signaling and its role in cancer progression. Studies were chosen based on their relevance to TWSG1’s dual role in TGF-β signaling and its implications for cancer treatment. Results: TWSG1 has been found to either enhance or inhibit TGF-β signaling. It can promote processes like epithelial-to-mesenchymal transition (EMT), cancer cell invasion, and metastasis by boosting interactions between TGF-β ligands and receptors and increasing SMAD protein phosphorylation. On the other hand, TWSG1 can also suppress TGF-β signaling by binding to the ligands, preventing them from interacting with receptors. High levels of TWSG1 are often associated with worse outcomes in several types of cancer, suggesting its potential as a biomarker and a target for cancer therapy. Conclusion: TWSG1 plays a complex role in TGF-β signaling that varies with the type of cancer and the surrounding environment. Targeting TWSG1, either alone or alongside TGF-β inhibitors, could offer new avenues for treating cancers driven by TGF-β signaling. More research is needed to fully understand how TWSG1 is regulated and to explore its potential for use in clinical settings.

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