CHI3L1 promotes cell division through activation of RhoA in lung cancer cells

Cytokinesis, the final stage of cell division, is crucial for maintaining genomic stability. Dysregulation of cytokinesis can contribute to cancer development. This study aimed to investigate the role of CHI3L1 in cytokinesis and its influence on lung cancer cell growth. We modulated CHI3L1 expression in lung cancer cells (overexpression and depletion) and normal cells, assessing effects on cytokinesis, mitotic duration, and actomyosin ring formation. In vivo studies were conducted using CHI3L1 knockout mice with tumor xenografts. Expression and activity of RhoA and Ect2 were analyzed using immunoblotting and immunohistochemistry. CHI3L1 overexpression in lung cancer cells accelerated cytokinesis, shortened mitosis, and enhanced cell proliferation. Conversely, CHI3L1 depletion in A549 cells increased multinucleation, impaired furrow formation, prolonged mitosis, and caused abnormal cytokinesis. Normal cells were less affected by CHI3L1 modulation. Mechanistically, CHI3L1 promoted formation and contraction of the actomyosin ring via RhoA and Ect2, effects more pronounced in cancer cells. In CHI3L1 knockout mice, tumor tissues exhibited reduced RhoA activity and Ect2 expression. CHI3L1 functions as a novel regulator of cytokinesis, promoting actomyosin ring formation and efficient mitosis, particularly in cancer cells. Its elevated expression in NSCLC and its influence on RhoA and Ect2 suggest that CHI3L1 may serve as a potential therapeutic target for disrupting aberrant cytokinesis in cancer.