Identification of the oncogenic role of centromere protein M in non-small cell lung cancer via CDC20/MYBL2/Wnt signaling pathways

J Mol Histol. 2025 Apr 26;56(3):144. doi: 10.1007/s10735-025-10423-5.

Abstract

Lung cancer remains the most prevalent carcinoma with a high mortality rate, yet the underlying mechanisms driving pulmonary neoplasia and disease progression are not fully understood. In our study, we conducted a comprehensive analysis of the transcriptome profiles and clinicopathological characteristics of 515 patients diagnosed with non-small cell lung cancer (NSCLC) from the TCGA database. We identified a significant upregulation of centromere protein M (CENPM) in NSCLC tissues, which was positively correlated with poor prognosis. Furthermore, overexpression of CENPM markedly promoted cell proliferation and increased the tumorigenic potential of NSCLC cell lines (A549/NCI-H1299), leading to accelerated tumor progression and reduced survival time in tumor-bearing mice. Mechanistically, CENPM activated the Wnt/β-catenin signaling pathway via the cell division cycle 20 (CDC20)/MYB proto-oncogene-like 2 (MYBL2) axis. Inhibition of either Wnt signaling or the CDC20/MYBL2 axis attenuated the tumorigenic potential and proliferative effects induced by CENPM. Our findings underscore the critical role of CENPM in driving NSCLC development and suggest that CENPM could serve as a novel biomarker for predicting NSCLC progression in clinical settings.

Keywords: CDC20; CENPM; MYBL2; Wnt signaling.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cdc20 Proteins* / genetics
  • Cdc20 Proteins* / metabolism
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Male
  • Mice
  • Prognosis
  • Proto-Oncogene Mas
  • Trans-Activators* / genetics
  • Trans-Activators* / metabolism
  • Wnt Signaling Pathway* / genetics

Substances

  • Proto-Oncogene Mas
  • Cell Cycle Proteins
  • MAS1 protein, human
  • Cdc20 Proteins
  • MYBL2 protein, human
  • Trans-Activators
  • CDC20 protein, human