TNNT3 as a candidate node in breast cancer mechanobiology: current evidence, mechanistic models, and key knowledge...

Breast cancer progression is increasingly recognized as a mechanically regulated process shaped by reciprocal interactions between tumor cells and the tumor microenvironment (TME). Mechanotransduction, cytoskeletal remodeling, cell-matrix adhesion, and extracellular matrix reorganization all contribute to tumor growth, invasion, and metastatic dissemination. TnT3, traditionally known as a component of the troponin (Tn) complex involved in striated muscle contraction, has recently attracted attention beyond its canonical role. In our previous study, we identified a significant genetic association between TNNT3 and triple-negative breast cancer (TNBC) using Mendelian randomization (SMR) analysis, colocalization (Coloc) analysis, and integrated gene expression profiling. In this review, we distinguish limited direct evidence in breast cancer from broader indirect mechanobiological support and from explicitly speculative models. Rather than proposing TNNT3 as a validated driver, we position it as a low-evidence but biologically interesting candidate whose relevance remains to be tested in spatially and cell-type-resolved systems.