Keratin 17 activates AKT signalling and induces epithelial-mesenchymal transition in oesophageal squamous cell carcinoma

Abstract

Oesophageal squamous cell carcinoma (ESCC) is an aggressive malignancy and a leading cause of cancer-related death worldwide. Lack of effective early diagnosis strategies and ensuing complications from tumour metastasis account for the majority of ESCC death. Thus, identification of key molecular targets involved in ESCC carcinogenesis and progression is crucial for ESCC prognosis. In this study, four pairs of ESCC tissues were used for mRNA sequencing to determine differentially expressed genes (DEGs). 347 genes were found to be upregulated whereas 255 genes downregulated. By screening DEGs plus bioinformatics analyses such as KEGG, PPI and IPA, we found that there were independent interactions between KRT family members. KRT17 upregulation was confirmed in ESCC and its relationship with clinicopathological features were analysed. KRT17 was significantly associated with ESCC histological grade, lymph node and distant metastasis, TNM stage and five-year survival rate. Upregulation of KRT17 promoted ESCC cell growth, migration, and lung metastasis. Mechanistically, we found that KRT17-promoted ESCC cell growth and migration was accompanied by activation of AKT signalling and induction of EMT. These findings suggested that KRT17 is significantly related to malignant progression and poor prognosis of ESCC patients, and it may serve as a new biological target for ESCC therapy. SignificanceOesophageal cancer is one of the leading causes of cancer mortality worldwide and oesophageal squamous cell carcinoma (ESCC) is the major histological type of oesophageal cancer in Eastern Asia. However, the molecular basis for the development and progression of ESCC remains largely unknown. In this study, RNA sequencing was used to establish the whole-transcriptome profile in ESCC tissues versus the adjacent non-cancer tissues and the results were bioinformatically analysed to predict the roles of the identified differentially expressed genes. We found that upregulation of KRT17 was significantly associated with advanced clinical stage, lymph node and distant metastasis, TNM stage and poor clinical outcome. Keratin 17 (KRT17) upregulation in ESCC cells not only promoted cell proliferation but also increased invasion and metastasis accompanied with AKT activation and epithelial-mesenchymal transition (EMT). These data suggested that KRT17 played an important role in ESCC development and progression and may serve as a prognostic biomarker and therapeutic target in ESCC.