CDK11 Promotes Paclitaxel Resistance in Cervical Cancer by Regulating LATS1 ‐Mediated Hippo Signaling Pathway Through Phosphorylation of NF2

Paclitaxel (PTX) is a first-line chemotherapeutic agent for cervical cancer, but resistance remains a major clinical challenge. This study investigates the role of cyclin-dependent kinase 11 (CDK11) in mediating PTX resistance and explores its underlying molecular mechanisms. Cell viability, proliferation, and apoptosis were measured using CCK8, EdU staining, colony formation, and flow cytometry, respectively. The transcriptional activity of YAP/TEAD was assessed using a dual luciferase reporter gene assay, and LATS1 ubiquitination level was assessed using an IP assay. The binding relationships between CDK11, CCNL2, and NF2 were examined by co-IP assay. PTX resistance was further investigated in xenograft mouse models. Our results showed that CDK11 expression was significantly elevated in PTX-resistant cervical cancer tissues and cells, and its knockdown markedly reduced PTX resistance in cervical cancer cells. Mechanically, CDK11 inactivated the Hippo signaling pathway by promoting CRL4-mediated LATS1 ubiquitination degradation. Additionally, the CDK11/CCNL2 complex inactivated the Hippo signaling pathway by phosphorylating NF2 at the S518 site and further reducing the binding of NF2 and CRL4 in the nucleus. Finally, in vivo xenograft experiments validated that CDK11 knockdown sensitized cervical cancer cells to PTX by activating the Hippo signaling pathway through inhibiting NF2 phosphorylation at the S518 site. In conclusion, the CDK11/CCNL2 complex promoted PTX resistance in cervical cancer by phosphorylating NF2 at the S518 site, which further reduced the binding of NF2 and CRL4 in the nucleus and inactivated the Hippo signaling pathway by promoting CRL4-mediated LATS1 ubiquitination degradation.