MELK Predicts Poor Prognosis and Promotes Metastasis in Esophageal Squamous Cell Carcinoma Via Activating the NF-κB Pathway
| Autor: | Wanying Deng, Ying Zhong, Zixi Qin, Hui Liu, Peiwen Li, Baoyin Guo, Lihui Wang, Xueyun Zhong, Jiecheng Ye |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
Poor prognosis Esophageal Neoplasms business.industry NF-kappa B NF-κB Protein Serine-Threonine Kinases Prognosis medicine.disease Esophageal squamous cell carcinoma digestive system diseases Metastasis Gene Expression Regulation Neoplastic chemistry.chemical_compound Oncology chemistry Cell Movement Cell Line Tumor Cancer research Animals Humans Medicine Esophageal Squamous Cell Carcinoma business Cell Proliferation |
| Popis: | Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide with a low 5-year survival rate due to the lack of effective therapeutic strategies. Accumulating evidence has indicated that Maternal embryonic leucine zipper kinase (MELK) is highly expressed in several tumors and correlates with tumor development. However, the biological effects of MELK in ESCC are still unknown.Methods: We used data from ESCC patient tissue specimens and online datasets to evaluate differences in MELK expression between paired carcinoma. Two ESCC cell lines were selected and MELK was stably knocked down by small hairpin RNA (shRNA) of MELK. Cell phenotypical experiments and animal metastasis assays were performed to detect the influence of MELK knockdown in vitro and in vivo. The potential molecular mechanism of MELK-mediated ESCC metastasis was further investigated by Western blotting and Immunofluorescence staining.Results: In this study, the expression of MELK in human ESCC tissues was higher than that in adjacent normal tissues and was positively correlated with the poor prognosis of patients. Reducing MELK expression resulted in growth inhibition and suppression of the invasive ability of ESCC cells in vitro and in vivo. MELK inhibition induced alterations of epithelial-to-mesenchymal transition associated proteins. Mechanistically, MELK interacted with IκB kinase (IKK) and promoted the phosphorylation of IKK, by which MELK regulated activation of the NF-κB pathway.Conclusions: Collectively, our study reveals the function and mechanism of MELK in the cell metastasis of ESCC, which may be a potential therapeutic target for ESCC. |
| Databáze: | OpenAIRE |
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