A stiffness-gated YAP-β-catenin axis orchestrates AXIN2 expression in metastatic breast cancer.

ABSTRACT: Breast cancer progression is strongly influenced by the mechanical properties of the tumor microenvironment, yet how extracellular matrix stiffness coordinates signaling between YAP and β-catenin remains unclear. Using breast cancer cells cultured on soft and stiff 2D substrates and 3D Matrigel spheroids, we show that the rigid matrices drive joint nuclear localization of YAP and β-catenin, whereas compliant environments reveal a compensatory increase in β-catenin nuclear entry following YAP depletion. However, this increase is insufficient to activate canonical Wnt targets, and AXIN2 emerges as a stiffness-sensitive gene requiring cooperative input from both regulators. Cytoskeletal tension and cell density further tune this interplay, indicating that mechanical and architectural cues joi

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12796759 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature