J Cancer 2020; 11(4):819-825. doi:10.7150/jca.36316

Research Paper

FGF14 Functions as a Tumor Suppressor through Inhibiting PI3K/AKT/mTOR Pathway in Colorectal Cancer

Tianhong Su1*, Linlin Huang2,3*, Ning Zhang2*, Sui Peng2,4,5, Xiaoxing Li5, Guangyan Wei1, Ertao Zhai6, Zhirong Zeng2, Lixia Xu5,7✉

1. Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;
2. Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;
3. Department of Gastroenterology and Hepatology, Guangdong Provincial People's Hospital/Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China;
4. Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;
5. Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
6. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;
7. Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong, China
*These authors contribute equally to the study.

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Citation:
Su T, Huang L, Zhang N, Peng S, Li X, Wei G, Zhai E, Zeng Z, Xu L. FGF14 Functions as a Tumor Suppressor through Inhibiting PI3K/AKT/mTOR Pathway in Colorectal Cancer. J Cancer 2020; 11(4):819-825. doi:10.7150/jca.36316. Available from http://www.jcancer.org/v11p0819.htm

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Abstract

We identified that Fibroblast Growth Factor 14 (FGF14) was preferentially methylated in colorectal cancer (CRC). In this study, we aimed to investigate the epigenetic regulation, biological function and molecular mechanism of FGF14 in CRC. The expression of FGF14 in CRC cell lines, normal human colon epithelial cell line, CRC tissues and paired adjacent normal tissues was detected by PCR and Western blot. The biological function of FGF14 in CRC was interrogated by cell viability assay, colony formation, flow cytometry, cell invasion and migration assay, as well as in vivo study. We found FGF14 was downregulated or silenced in all (10/10) CRC cell lines, while it was expressed in normal colonic tissues and normal human colon epithelial cell line. The expression of FGF14 was lower in primary CRCs as compared to their adjacent normal tissues. Significant higher methylation of FGF14 was observed in CRCs than that in normal tissues based on the data from TCGA database. The loss of FGF14 gene expression was restored by treatment with DNA methyltransferase inhibitor 5-Aza. Re-expression of FGF14 in CRC cell lines inhibited cell viability and colony formation, and induced cell apoptosis. FGF14 induced mitochondrial apoptosis and inhibited PI3K/AKT/mTOR pathway. In xenograft mouse model, overexpression of FGF14 significantly reduced tumor growth (P<0.001). In conclusion, FGF14 is a novel tumor suppressor, which suppresses cell proliferation and induces cell apoptosis via mediating PI3K/AKT/mTOR pathway.

Keywords: FGF14, DNA methylation, tumor suppressor, apoptosis, colorectal cancer