title: DEK depletion negatively regulates Rho/ROCK/MLC pathway in non-small cell lung cancer.
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.
authors.affiliation: Department of Pathology, The First Afﬁliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Wang
authors.forename: Limei
authors.initials: L
authors.lastname: Sun
authors.forename: Mingyue
authors.initials: M
authors.lastname: Yang
authors.forename: Wenting
authors.initials: W
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Zihui
authors.initials: Z
authors.lastname: Liu
authors.forename: Xueshan
authors.initials: X
authors.lastname: Qiu
authors.forename: Enhua
authors.initials: E
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D024722:Cardiac Myosins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018994:Myosin Light Chains / Q000378:metabolism*; D015513:Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C000715470:MAS1 protein, human; D018994:Myosin Light Chains; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000090063:Proto-Oncogene Mas; C107184:myosin light chain 2; D054460:rho-Associated Kinases; D024722:Cardiac Myosins; D020742:rhoA GTP-Binding Protein
keywords: DEK; RhoA; apoptosis; migration; oncogenic; proliferation