Multifaceted role of transgelin isoforms in cancer hallmarks

Abstract Transgelins (TAGLNs) are actin-binding proteins within the calponin family, playing a crucial role in modulating actin-myosin interactions and maintaining actin filament stability. These proteins are expressed in both smooth and non-smooth muscle cells, contributing to the regulation of muscle contractility and cell migration. TAGLNs family has three isoforms that differ in their isoelectric point, namely: TAGLN1, TAGLN2, and TAGLN3. TAGLNs regulation is involved in the development of many diseases, such as pulmonary arterial hypertension, asthma, atherosclerosis, obstructive nephropathy, diabetes, and cancer. Recent research indicates TAGLNs involvement in carcinogenesis and chemoresistance. This review investigates TAGLNs as potential cancer biomarkers, exploring their versatile tissue-specific impact on patient outcomes. We also highlight their roles as, tumor suppressor agents and tumor progression oncogenes depending on the tumor type, tumor genetic variations and TAGLNs expression profiles. Furthermore, emerging evidence suggests that the interplay between TAGLN2 and chemoresistance to anticancer drugs is mediated by its interaction with the chemoresistance double agent MT-2, with possible bidirectional implications. TAGLNs present a promising avenue for novel therapeutic strategies against cancer, owing to their tissue-specific duality in promoting/suppressing tumor growth and cell migration in cancer cells. Thus, they can serve as a potential prognostic/diagnostic biomarker. The focus should be on leveraging, in future therapeutics, the interplay between TAGLNs and MTs to reverse tumor progression and chemoresistance, transforming them into tumor suppression.