Yixuan Wang1, Wensheng Qiu1, Ning Liu1, Libin Sun1, Zhao Liu1, Shasha Wang1, Peng Wang2, Shihai Liu3, Jing Lv1. 1. Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266071, China. 2. Department of Oncology, Weifang Yidu Central Hospital, Qingzhou 262500, China. 3. Central Laboratory, the Affiliated Hospital of Qingdao University, Qingdao 266071, China.
Abstract
BACKGROUND: Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC. METHODS: We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy. RESULTS: We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC. FOXK1 promotes the malignant behavior of GC by regulating autophagy via activation of the class I phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and inhibition of the expression of class III PI3K. CONCLUSIONS: These findings provide a new target for the comprehensive treatment of GC by highlighting the relationship between FOXK1 and malignant behaviors in GC. 2020 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Forkhead box K1 (FOXK1) is a transcription factor that contributes to cancer development, but it is unclear how FOXK1 regulates the proliferation and migration of gastric cancer (GC) cells. The purpose of this study was to investigate the clinical significance, biological function, and molecular mechanisms of FOXK1 in GC. METHODS: We conducted bioinformatics assays and western blotting to assess FOXK1 expression. Then, we performed immunohistochemistry (IHC) with tissue microarrays (TMAs) to assess FOXK1 expression in order to identify an association between FOXK1 expression levels and clinical parameters. We used 5-ethynyl-2'-deoxyuridine (EdU), wound healing and Transwell assays to determine whether FOXK1 promotes malignant behaviors in GC. Furthermore, immunofluorescence staining, transmission electron microscopy and western blotting were used to verify an association between FOXK1 and autophagy. RESULTS: We observed high levels of FOXK1 expression in GC tissues, which were associated with the degree of malignancy in GC. FOXK1 promotes the malignant behavior of GC by regulating autophagy via activation of the class I phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway and inhibition of the expression of class III PI3K. CONCLUSIONS: These findings provide a new target for the comprehensive treatment of GC by highlighting the relationship between FOXK1 and malignant behaviors in GC. 2020 Annals of Translational Medicine. All rights reserved.
Entities:
Keywords:
3-methyladenine (3-MA); Forkhead box K1 (FOXK1); autophagy; gastric cancer
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