FOXK2 suppresses the malignant phenotype and induces apoptosis through inhibition of EGFR in clear‐cell renal cell carcinoma. Issue 12 (14th February 2018)

• Record Type: Journal Article
• Authors: Zhang, Fan; Ma, Xin; Li, Hongzhao; Zhang, Yu; Li, Xintao; Chen, Luyao; Guo, Gang; Gao, Yu; Gu, Liangyou; Xie, Yongpeng; Duan, Junyao; Zhang, Xu
• Is Part Of: International journal of cancer. Volume 142:Issue 12(2018)
• Page Start: 2543
• Page End: 2557
• Publication Date: 2018-02-14
• Subjects: clear‐cell renal cell carcinoma -- FOXK2 -- apoptosis -- EGFR; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31278
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : Forkhead box K2 (FOXK2) belongs to the forkhead box transcription factor family. Recent studies have revealed that FOXK2 plays essential roles in cancer cell proliferation and survival. However, the biological function of FOXK2 in renal cell carcinoma remains unexplored. In our study, we demonstrated that FOXK2 mRNA and protein levels were decreased in clear‐cell renal cell carcinoma (ccRCC) tissues compared to those in corresponding non‐tumor renal tissues, and decreased FOXK2 levels were associated with poor prognosis in ccRCC patients after nephrectomy. FOXK2 suppressed proliferation, migration and invasion capabilities of ccRCC cells and induced cellular apoptosis in vitro . Moreover, we found that FOXK2 overexpression inhibited xenograft tumor growth and promoted apoptosis in vivo . Genome‐wide transcriptome profiling using FOXK2 overexpressed 769‐P cells revealed that the epidermal growth factor receptor (EGFR) was a potential downstream gene of FOXK2. Overexpression of EGFR is able to rescue the inhibited proliferation capacity and the enhanced apoptosis capacity due to the overexpression of FOXK2 in 769‐P cells. Collectively, our results indicate that FOXK2 inhibits the malignant phenotype of ccRCC and acts as a tumor suppressor possibly through the inhibition of EGFR. Abstract : What's new? Forkhead box K2 (FOXK2) is involved in various molecular processes and is reported to play a role in breast and colorectal carcinogenesis. In addition, the related factor, FOXO3a, is critical to metastasis in clear‐cell renal cell carcinoma (ccRCC). Whether FOXK2 also has a role in ccRCC, however, is unknown. Here, FOXK2 expression is shown to be downregulated in ccRCC, with reduced levels of FOXK2 mRNA associated with poor prognosis. In ccRCC cells, FOXK2 overexpression inhibited ccRCC cell proliferation, migration, and invasion and induced apoptosis, possibly through EGFR inhibition. The findings suggest that FOXK2 functions as a tumor suppressor in ccRCC.