From Tumor Suppressor to Tumor Promoter - The Dual Role of LIMCH1 in Cancer and Its Clinical Implications.

LIM and Calponin Homology Domain 1 (LIMCH1) is a multi-domain protein-coding gene located on human chromosome 4p13. Its encoded protein participates in the dynamic regulation of the actin cytoskeleton through an N-terminal calponin homology domain and a C-terminal LIM domain. LIMCH1 specifically binds to non-muscle myosin IIA (NM-IIA). This binding enhances the dual phosphorylation of myosin regulatory light chains. As a result, it increases the adenosine triphosphatase (ATPase) activity and assembly efficiency of NM-IIA, stabilizes stress fibers, promotes focal adhesion maturation, and inhibits cell migration. Recent studies have revealed that LIMCH1 exhibits context-dependent dual functions in cancer. For example, it acts as a tumor suppressor in lung cancer, as well as in clear cell renal cell carcinoma and oral squamous cell carcinoma. In contrast, it displays pro-oncogenic phenotypes in breast cancer and cervical cancer. This functional heterogeneity may be regulated by multiple mechanisms, including gene fusion, alternative splicing, post-translational modifications, and tumor-specific interaction networks. Bioinformatics analyses further indicate that LIMCH1 is differentially expressed in multiple solid tumors, and its high expression is significantly enriched in epithelial-mesenchymal transition pathways, suggesting an important role in tumor metastasis. This review systematically summarizes the molecular structure, biological functions, and dual regulatory effects of LIMCH1 in cancer, and explores its potential clinical applications as a novel tumor biomarker and therapeutic target.