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

Min Wei1,2, Xuefei Bai1,3, Lili Xi4

  • 1The First Clinical Medical College of Lanzhou University, Lanzhou, China.

Abstract

Insights

Cytoskeleton-associated protein 2-like (CKAP2L) promotes endometrial cancer (EC) growth and spread by stabilizing AKT signaling. Targeting CKAP2L may offer a new therapeutic strategy for EC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cytoskeleton-associated protein 2-like (CKAP2L) is a microtubule-associated protein implicated as an oncogene in various cancers.
  • Its specific role and mechanism in endometrial cancer (EC) remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of CKAP2L in endometrial cancer (EC) pathogenesis.
  • To explore the underlying molecular mechanisms by which CKAP2L influences EC progression.

Main Methods:

  • Bioinformatics analysis correlated CKAP2L expression with clinical features.
  • Immunohistochemistry assessed protein levels in EC tissues.
  • In vitro and in vivo models evaluated CKAP2L's impact on EC cell proliferation, migration, invasion, apoptosis, and cell cycle.
  • Western blotting and co-immunoprecipitation assays examined CKAP2L's interaction with AKT and its ubiquitination status.

Main Results:

  • CKAP2L expression was significantly elevated in EC tissues.
  • CKAP2L knockdown inhibited EC cell growth, proliferation, migration, invasion, and F-actin formation, while inducing apoptosis and cell cycle arrest.
  • CKAP2L overexpression promoted malignant phenotypes.
  • CKAP2L stabilized phosphorylated AKT (p-AKT) by inhibiting its ubiquitination and proteasomal degradation, thereby activating the PI3K/AKT signaling pathway.

Conclusions:

  • CKAP2L enhances malignant behavior and actin cytoskeleton remodeling in EC cells.
  • This occurs through decreased AKT ubiquitination, sustained AKT phosphorylation, and activation of the PI3K/AKT pathway.
  • CKAP2L represents a potential therapeutic target for endometrial cancer.

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