New insights into the role of TWIST1 in breast cancer progression and metastasis.

The transcription factor TWIST1 plays a fundamental role in the regulation of breast cancer initiation, progression, metastasis, and resistance to treatment. As a prominent driver of epithelial-mesenchymal transition (EMT), TWIST1 promotes phenotypic plasticity in cancer cells, enabling enhanced invasion, migration, and metastatic colonization. In addition, TWIST1 supports the maintenance of cancer stem cell (CSC) traits, which contribute to intratumoral heterogeneity and the likelihood of tumor relapse. Abnormal activation of TWIST1 stimulates stemness-related programs through the regulation of essential signaling pathways and stem cell markers, thereby functionally linking EMT with mechanisms of self-renewal and therapeutic resistance. The regulation of TWIST1 is highly complex and occurs at multiple levels, including epigenetic control, non-coding RNA-mediated regulation, transcriptional modulation, and post-translational modifications. Interactions with major oncogenic signaling cascades and signals originating from the tumor microenvironment further enhance its contribution to cancer progression. Increasing clinical evidence indicates that elevated TWIST1 expression is associated with poor clinical outcomes, higher metastatic burden, and reduced treatment efficacy, emphasizing its importance as a prognostic biomarker and a potential therapeutic target in breast cancer management.