Multifaceted role of transgelin isoforms in cancer hallmarks.

This article focuses on transgelins (TAGLNs), a family of actin-binding proteins with three isoforms—TAGLN1, TAGLN2, and TAGLN3—that regulate actin cytoskeleton dynamics and are implicated in various diseases, notably cancer. TAGLNs exhibit dual roles in cancer, acting as tumor suppressors or oncogenes depending on the isoform, cancer type, and expression profile, with TAGLN1 often linked to tumor suppression and TAGLN2 frequently associated with tumor progression, metastasis, and chemoresistance. Emerging evidence highlights the interaction between TAGLN2 and metallothionein-2 (MT-2), a protein involved in metal homeostasis, suggesting their synergistic role in cancer development and resistance to chemotherapy. The review underscores the potential of TAGLNs as prognostic biomarkers and therapeutic targets, advocating for future research to exploit the TAGLNs–MT interplay to counteract tumor progression and chemoresistance in a tissue-specific manner.