CHI3L1 promotes proliferation and metastasis of ovarian cancer cells

On the other hand, CHI3L1 binds to and stabilizes protein arginine methyltransferase 5 (PRMT5) in tumor cells, thereby enhancing its methyltransferase activity. This upregulation suppresses dual-specificity phosphatase 1 (DUSP1), a phosphatase of mitogen-activated protein kinase (MAPK), and sustains oncogenic MAPK signaling across multiple tumor models. Obesity amplifies this pathway by heightening HIF-1α activity and elevating CHI3L1 levels in adipose tissue, which drives both tumor progression and resistance to anti-angiogenic therapy.

Pharmacological inhibition of CHI3L1 disrupts this signaling loop and restores therapeutic sensitivity, while also alleviating immune exhaustion in the tumor microenvironment. Collectively, our findings establish CHI3L1 as a key mediator of a unified mechanism that drives omental tropism and obesity-associated aggressive phenotypes, highlighting its potential as a prognostic biomarker and therapeutic target to improve anti-angiogenic therapy.