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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.
Abstract:
The human DEK proto-oncogene is a nuclear protein with suspected roles in human carcinogenesis. DEK appears to function in several nuclear processes, including transcriptional regulation and modulation of chromatin structure. To investigate the clinicopathological significance of DEK in patients with non-small cell lung cancer (NSCLC), we analyzed DEK immunohistochemistry in 112 NSCLC cases. The results showed that DEK was overexpressed mainly in the nuclear compartment of tumor cells. In squamous cell carcinoma, DEK-positive expression occurred in 47.9% (23/48) of cases, and in lung adenocarcinoma, DEK-positive expression occurred in 67.2% (43/64) of cases and correlated with differentiation, p-TNM stage, and nodal status. Moreover, in lung adenocarcinoma, DEK expression was significantly higher compared with DEK expression in squamous cell carcinoma. Kaplan-Meier analysis showed that patients with low DEK expression had higher overall survival compared with patients with high DEK expression. Depleting DEK expression inhibited cellular proliferation and migration. Furthermore, in DEK-depleted NSCLC cells, we found that RhoA expression was markedly reduced; in conjunction, active RhoA-GTP levels and the downstream effector phosphorylated MLC2 were also reduced. Taken together, DEK depletion inhibited cellular migration in lung cancer cell lines possibly through inactivation of the RhoA/ROCK/MLC signal transduction pathway.
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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