DEK depletion negatively regulates Rho/ROCK/MLC pathway in non-small cell lung cancer

Junying Wang1, Limei Sun, Mingyue Yang

  • 1Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.

Insights

The DEK proto-oncogene is overexpressed in non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma. Lower DEK expression correlates with better survival, suggesting DEK as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The DEK proto-oncogene is a nuclear protein implicated in human carcinogenesis.
  • DEK plays roles in transcriptional regulation and chromatin structure modulation.
  • Its clinicopathological significance in non-small cell lung cancer (NSCLC) requires investigation.

Purpose of the Study:

  • To investigate the clinicopathological significance of DEK in NSCLC patients.
  • To explore the role of DEK in NSCLC cell proliferation and migration.
  • To elucidate the molecular mechanisms underlying DEK's function in lung cancer.

Main Methods:

  • Immunohistochemistry was used to analyze DEK expression in 112 NSCLC cases.
  • DEK expression levels were correlated with clinicopathological features and patient survival.
  • Cellular proliferation, migration assays, and Western blotting were performed in DEK-depleted NSCLC cells.

Main Results:

  • DEK was overexpressed in the nucleus of NSCLC tumor cells, with higher prevalence in lung adenocarcinoma (67.2%) than squamous cell carcinoma (47.9%).
  • DEK expression in lung adenocarcinoma correlated with differentiation, p-TNM stage, and nodal status.
  • Kaplan-Meier analysis revealed that low DEK expression was associated with higher overall survival.
  • DEK depletion inhibited NSCLC cell proliferation and migration, reducing RhoA-GTP and phosphorylated MLC2 levels, indicating RhoA/ROCK/MLC pathway inactivation.

Conclusions:

  • DEK is significantly overexpressed in NSCLC, particularly lung adenocarcinoma, and serves as a prognostic marker.
  • DEK depletion inhibits NSCLC cell proliferation and migration.
  • The RhoA/ROCK/MLC signaling pathway is implicated in DEK-mediated cellular migration in lung cancer.

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