Mechano-regulation of proline metabolism and cancer progression by kindlin-2.

Alterations of cell mechano-environment and metabolism are common features of malignant neoplasm. We recently showed that increased stiffness of extracellular matrix is intrinsically linked to up-regulation of proline synthesis through a mechano-responsive fermitin family homolog 2 (FERMT2, best known as kindlin-2) and pyrroline-5-carboxylate reductase 1(PYCR1) complex, which in turn promotes collagen matrix synthesis, cell proliferation, survival, and cancer progression.