FHL2 enhances ITGB1-mediated ECM remodeling and cellular stiffness to promote radioresistance in non-small cell lung cancer.

ABSTRACT: Radiotherapy is a cornerstone treatment for non-small cell lung cancer (NSCLC), but its efficacy is frequently limited by tumor-intrinsic radioresistance. Cellular stiffness and extracellular matrix (ECM) interactions are critical mechanisms underlying this resistance. The adaptor protein four-and-a-half LIM domains 2 (FHL2) has emerged as a key regulator of tumor radioresistance. This study elucidates the role of FHL2 in enhancing radioresistance in NSCLC through ECM remodeling and cellular stiffness. FHL2 was found to promote cell survival, DNA damage repair, and ECM remodeling in response to irradiation, with its interaction with integrin β1 (ITGB1) playing a pivotal role. Depletion of FHL2 significantly reduced cell survival and radioresistance in radioresistant NSCLC cell lines, while

SUBMITTER: Pu X 

PROVIDER: S-EPMC12552696 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature