Significance of death-associated protein kinase expression in esophageal squamous cell carcinoma

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a deadly disease with the poor prognosis in the world. The distal metastasis is the most death reason of ESCC. It is needed to have a comprehensive understanding of the molecular mechanism of metastasis to increase the free survive rate. T-LAK cell-originated protein kinase (TOPK) which is a MAPKK-like kinase takes an vital role in many physical and pathophysiological progress. However, the function of TOPK in ESCC metastasis was unclear. Methods Tissue array was used to evaluate the relationship between TOPK and ESCC patient with lymph node metastasis. Wound healing assay, transwell assay and lung metastasis mice model were assessed for the role of TOPK in the migration of ESCC cells in vitro and in vivo respectively. Protein kinase array, MS and molecular modeling were carried out to find the relational pathways and target protein of TOPK. Even, immune-fluorescence and western blot were performed to evaluate the mechanism of TOPK. Results We found that the high level of TOPK was correlated with the aggressive phenotype in ESCC tissues. Knocking down TOPK inhibited the invasion and migration of ESCC cells. We also verified that TOPK inhibitor HI-TOPK-032 inhibited the lung metastasis in ESCC cell exnograft model. Even more, molecular investigation indicated that TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway by binding with γ-catenin. Conclusion These findings reveal that TOPK was sincerely related with ESCC cell metastasis and TOPK promoted the invasion of ESCC cells by activing Src/GSK3β/STAT3, ERK pathway. This means that TOPK may be a potential molecular target for ESCC in clinic.

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Correlation of P38 Mitogen-Activated Protein Kinase Expression to Clinical Stage in Nasopharyngeal Carcinoma

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2018.355 ◽

2018 ◽

Vol 6 (11) ◽

pp. 1982-1985 ◽

Cited By ~ 2

Author(s):

Farhat Farhat ◽

Elvita Rahmi Daulay ◽

Jessy Chrestella ◽

Rizalina Arwinati Asnir ◽

Ashri Yudhistira ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Protein Kinase ◽

Nasopharyngeal Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Clinical Stage ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Keratinizing Squamous Cell Carcinoma ◽

Kinase Expression

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon and usually diagnosed at the advanced stage. A subfamily of mitogen-activated protein kinase which is called p38 mitogen-activated protein kinase (MAPK) involved in response to stress, and plays an important role in cell regulation. There is a suggestion that p38 mitogen-activated protein kinase could be a potential biomarker to determine the clinical stage of nasopharyngeal carcinoma. AIM: The aim of this study is for observing and analysing the correlation of p38 mitogen-activated protein kinase expression in regards to nasopharyngeal carcinoma patient’s clinical stage. METHODS: This study involved 126 nasopharyngeal carcinoma patients admitted to Haji Adam Malik General Hospital. RESULTS: The result of this study indicates that nasopharyngeal carcinoma mostly found in the age group 41-60 years, male, non-keratinizing squamous cell carcinoma, and stage IV group. In immunohistochemistry evaluation, most of p38 mitogen-activated protein kinase overexpressed in non-keratinizing squamous cell carcinoma, T3-T4, N2-N3 and clinical stage III-IV. Spearman’s test for categorical correlation yield p-value of < 0.001. CONCLUSION: In conclusion, there is a significant correlation between p38 mitogen-activated protein kinase expression and the clinical stage of nasopharyngeal carcinoma.

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