2. Academic Validation
  3. USP13 exacerbates the malignant progression of cervical cancer by inhibiting ECT2 ubiquitination and degradation

USP13 exacerbates the malignant progression of cervical cancer by inhibiting ECT2 ubiquitination and degradation

  • Reprod Biol. 2025 Nov 11;26(1):101095. doi: 10.1016/j.repbio.2025.101095.
Tingting Li 1,  Xiulan Xiong 2,  Tingting Xie 3,  Wei Liu 3,  Xuqin Feng 1,  Silin Chen 1,  Xin Hu 1,  Rengui Li 4,  Kaiwen Fu 5
Affiliations

Affiliations

  • 1 Department of Oncology, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong 637000, China.
  • 2 Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China; Department of Gynecologic Oncology Center, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.
  • 3 Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China; Department of Medical Laboratory, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.
  • 4 Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China; Department of Gynecologic Oncology Center, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China. Electronic address: [email protected].
  • 5 Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China. Electronic address: [email protected].
PMID: 41223669 DOI: 10.1016/j.repbio.2025.101095
Abstract

Cervical Cancer (CC) is one of the most common malignant tumors affecting the female reproductive system. Epithelial Cell Transforming Sequence 2 (ECT2), a guanine nucleotide exchange factor, is crucial in regulating cellular functions. This study focuses on elucidating the role of ECT2 in CC and the involved underlying mechanisms. Western blot verified protein expression in tissues and cells. Cell proliferation, migration, and invasion were assessed via clone formation, wound healing, and transwell assays. Glycolytic indicators (glucose uptake, lactate release, ATP levels, Lactate Dehydrogenase (LDH) activity, and pyruvate dehydrogenase (PDH) activity) were detected using specific kits. UbiBrowser was used to predict Ubiquitin-Specific Protease 13 (USP13)-mediated ECT2 deubiquitination. Co-immunoprecipitation (Co-IP) was performed to validate USP13's deubiquitination on ECT2 and their interaction. In vivo validation employed a mouse xenograft model, with immunohistochemistry (IHC) assessing gene expression therein. This study demonstrated that ECT2 was upregulated in CC tissues and cells, and its downregulation effectively inhibited the proliferation, migration, invasion, and glycolysis of CC cells. USP13 exhibited high expression levels in CC and stabilized ECT2 expression through its deubiquitinating activity. Knockdown of USP13 significantly suppressed the malignant phenotypes of CC cells; however, this suppressive effect was markedly reversed upon ECT2 overexpression. In vivo experiments revealed that USP13 knockdown suppressed CC tumor growth by modulating ECT2 expression. Together, USP13 exacerbates the malignant progression of CC by inhibiting ECT2 ubiquitination, suggesting that targeting the USP13-ECT2 axis might be a potential therapeutic strategy for CC with notable clinical significance.

Keywords

Cervical cancer; Epithelial cell transforming sequence 2; Malignant progression; Ubiquitin-specific protease 13.

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