What question did this study set out to answer?

This study aims to clarify the role of CKAP2L in endometrial cancer and its mechanisms of action.

May 24, 2026Open Access

CKAP2L promotes endometrial cancer progression by suppressing AKT ubiquitination and activating the PI3K/AKT signaling pathway

Key Points

This study aims to clarify the role of CKAP2L in endometrial cancer and its mechanisms of action.
Analyzed CKAP2L correlation with clinical features using bioinformatics.
Performed in vivo validation using xenograft mouse models.
Conducted various assays to assess CKAP2L's impact on cell behavior and signaling.
CKAP2L was upregulated in endometrial cancer tissues.
CKAP2L knockdown led to reduced cancer cell proliferation and increased apoptosis.
Overexpression of CKAP2L stabilized p-AKT by inhibiting its ubiquitination, activating the PI3K/AKT pathway.

Abstract

Objective Cytoskeleton-associated protein 2-like (CKAP2L), a microtubule-associated protein that serves as a structural component of the spindle pole and a cell cycle-related protein, acts as an oncogene in several cancers. This study seeks to elucidate the role of CKAP2L in endometrial cancer (EC) and to investigate its underlying mechanisms. Methods The correlation between CKAP2L and clinical features was analyzed utilizing bioinformatics approaches. The expression of CKAP2L, Ki-67, and PCNA was evaluated using immunohistochemistry. Xenograft mouse models were established for in vivo validation. Colony formation, EdU, CCK8, flow cytometry analysis, transwell, and scratch assays were performed to assess the impact of CKAP2L on EC cell malignant properties. The Phalloidin staining assay was used to evaluate actin cytoskeletal remodeling. The level of CKAP2L, Cleaved-Caspase-3, Bax, Bcl-2, CDK1, Cyclin B1, p27, p21, and PI3K/AKT was analyzed by Western blotting analysis. Co-immunoprecipitation (Co-IP) and ubiquitination assays were conducted to investigate the interaction between CKAP2L and AKT. Results CKAP2L was elevated in EC tissues. In vivo experiments revealed that CKAP2L knockdown attenuated EC growth. In vitro experiments showed CKAP2L depletion inhibited EC cell proliferation, migration, invasion, and F-actin formation, while triggering apoptosis and cell cycle arrest. Conversely, CKAP2L overexpression produced the opposite effects. Cycloheximide chase and MG132 assays revealed CKAP2L stabilized p-AKT by inhibiting ubiquitin-proteasome degradation. Overexpressing CKAP2L decreased AKT ubiquitination and activated PI3K/AKT signaling. Conclusions CKAP2L enhances the malignant behavior and actin cytoskeleton remodeling of EC cells by decreasing AKT ubiquitination, sustaining AKT phosphorylation, and activating the PI3K/AKT signaling pathway. This indicates that CKAP2L could be a promising therapeutic target for EC.

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