Overexpression of KRT17 promotes proliferation and invasion of non-small cell lung cancer and indicates poor prognosis

Abstract

Zhao Wang,1,2 Mai-Qing Yang,1,3 Lei Lei,1 Liang-Ru Fei,1 Yi-Wen Zheng,1 Wen-Jing Huang,1 Zhi-Han Li,1 Chen-Chen Liu,1 Hong-Tao Xu11Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Pathology, General Hospital of Heilongjiang Land Reclamation Bureau, Harbin 150088, People’s Republic of China; 3Department of Pathology, Changyi People’s Hospital, Changyi, People’s Republic of ChinaPurpose: Keratin 17 (KRT17) is a 48 KDa type I intermediate filament, which is mainly expressed in epithelial basal cells. KRT17 has been shown to be overexpressed in many malignant tumors and play an important role in the occurrence and development of tumors. Therefore, this study explored the role and underlying mechanism of KRT17 in non-small cell lung cancers (NSCLC).Methods: KRT17 expression and its correlations with clinicopathological factors were examined in lung cancer tissues by immunohistochemistry. The prognosis value of KRT17 in NSCLCs was retrieved from The Cancer Genome Atlas (TCGA) online databases. The expression level of KRT17 was increased or decreased by KRT17 gene transfection or small RNA interference in lung cancer cells, respectively. Further, proliferation and invasiveness of lung cancer cells were determined by cell proliferation and invasion assays, respectively. Finally, expression levels of proteins related to Wnt signaling pathways and epithelial mesenchymal transition (EMT) were detected by Western blot.Results: The expression level of KRT17 in NSCLCs was significantly higher than normal lung tissues. High expression of KRT17 predicted poor prognosis of patients with NSCLCs, especially lung adenocarcinomas, and was correlated with poor differentiation and lymphatic metastasis. Overexpression of KRT17 enhanced, while KRT17 knockdown inhibited, the proliferation and invasiveness of lung cancer cells. Overexpression of KRT17 up-regulated β-catenin activity and levels of Wnt target genes, such as cyclin D1, c-Myc, and MMP7. Moreover, KRT17 promoted EMT by up-regulating Vimentin, MMP-9, and Snail expression and down-regulating E-cadherin expression.Conclusion: Overexpression of KRT17 is common in NSCLCs and indicates poor prognosis. Overexpression of KRT17 enhances the proliferation and invasiveness of NSCLC cells by activating the Wnt signaling pathway and EMT process. KRT17 is a potential indicator of NSCLC progression and poor survival.Keywords: keratin 17, non-small cell lung cancer, Wnt signaling pathway, epithelial mesenchymal transition, proliferation, invasion

Keywords

• Keratin 17
• non-small cell lung cancer
• Wnt signaling pathway
• epithelial mesenchymal transition
• proliferation
• invasion