Coexpression of FOXK1 and vimentin promotes EMT, migration, and invasion in gastric cancer cells
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In human gastric cancer (GC), the upregulation of FOXK1 and vimentin is frequently observed in cancer cells and correlates with increased malignancy. We report that FOXK1 synergizes with vimentin to promote GC invasion and metastasis via the induction of epithelial-mesenchymal transition (EMT). We showed that higher expression levels of FOXK1 were significantly associated with GC development. FOXK1 can physically interact with and stabilize vimentin. Moreover, a positive correlation between the expression of FOXK1 and vimentin was found in GC cells. Higher expression levels of these two proteins were significantly associated with differentiation, lymph node metastasis, AJCC stage, and poorer prognosis. Furthermore, the coexpression of FOXK1 and vimentin enhances cell metastasis through the induction of EMT in GC cells. However, the siRNA-mediated repression of vimentin in FOXK1-overexpressing cells reversed the EMT-like phenotype and reduced GC cell migration and invasion in vitro and in vivo. Altogether, our findings suggest that the vimentin-FOXK1 axis provides new insights into the molecular mechanisms underlying EMT regulation during GC progression and metastasis.
KeywordsFOXK1 Vimentin Gastric cancer Metastasis Epithelial-mesenchymal transition
The forkhead box
American Joint Committee on Cancer
This study was supported by grants from the National Natural Science Funds of China (81672875 and 81772964) and “President Foundation of Nanfang Hospital, Southern Medical University” (2012B009, 2013Z007) and high-level topic-matching funds of Nanfang Hospital (201347 and G201227). Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University; Guangzhou Pilot Project of Clinical and Translational Research Center (early gastrointestinal cancer, No. 7415696196402).
Compliance with ethical standards
The authors declare that they have no conflict of interest.
This study was conducted with the approval of the ethics committee of Southern Medical University.
Provenance and peer review
Not commissioned; externally peer reviewed.
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