FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport
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PRIMARY RESEARCH
Cancer Cell International Open Access
FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport Wenying Tian1, Wenjia Zhang1, Yan Zhang2, Tianyue Zhu1, Yuting Hua1, Hui Li1, Qinglin Zhang1 and Min Xia1*
Abstract Background: The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear. The purpose of this study is to determine the effects of fatty acid binding protein 4 (FABP4), a transporter for lipids, on colon cancer progression. Methods: The distribution of lipids and FABP4 was tested in the colon cancer tissues and adjacent normal tissues, and their relationship was also verified in vitro. Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of FABP4 on the biological behaviors of colon cancer, and the positive results were checked in vivo. Meanwhile, the regulatory role of FABP4 in the energy and lipid metabolism was evaluated by the levels of triglyceride, ATP, LDH, glycerol and NEFA. At last, GO and KEGG analysis based on FABP4 overexpressed cells was performed, and the AKT pathway and epithelial–mesenchymal transition (EMT)-related proteins were determined by Western blot. Results: Higher accumulation of lipids and stronger FABP4 transcription were observed in colon cancer tissues. Having been incubated with adipose tissue extract and overexpressed FABP4, colon cancer cells demonstrated enhanced lipid accumulation. In functional experiments, co-culture with adipose tissue extract significantly enhanced the invasion and migration of colon cancer cells, as well as the energy and lipid metabolism, and all these processes were reversed by FABP4 inhibitor. In addition, the metastasis of FABP4-overexpressed colon cancer cells was also significantly enhanced in vitro and in vivo. In terms of mechanism, the bioinformatics analysis showed that FABP4 was enriched in 11 pathways related to metabolic processes in FABP4 overexpressed cells. Finally, FABP4 overexpression improved EMT progression of colon cancer, as evidenced by the upregulation of Snail, MMP-2 and MMP-9, the downregulation of E-cadherin. The expression of p-Akt was also elevated. Conclusion: FABP4 overexpression could increase FAs transport to enhance energy and lipid metabolism, and activate AKT pathway and EMT to promote the migration and invasion of colon cancer cells. Keywords: Colon cancer, Fatty acid binding protein 4, Metastasis, Lipid, Epithelial–mesenchymal transition, AKT Background Colon cancer is a common malignant tumor worldwide. About 1,200,000 new cases and more than *Correspondence: [email protected] 1 Department of Gastroenterology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, 299 Qing Yang Road, Wuxi 214023, Jiangsu, People’s Republic of China Full list of author information is available at the end of the article
600,000 related deaths are reported annually [1]. Recent studies have shown the critical role of tumor microenvironment in the invasion and
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