Abstract
BackgroundThe 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.MethodsThe 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.ResultsHigher 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.ConclusionFABP4 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.
Highlights
The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear
Lipid accumulation in colon cancer cells was related to fatty acid binding protein 4 (FABP4)‐mediated Fatty acid (FA) transport through the transmembrane To explore the distribution of lipids in colon cancer tissues, we stained the frozen tissue sections with oil red O solution
Similar results were seen in HCT-116 cells. These results indicated that FABP4 enhanced the epithelial–mesenchymal transition (EMT) in colon cancer cells, probably through AKT pathway
Summary
The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear. Recent studies have shown the critical role of tumor microenvironment in the invasion and metastasis of cancers [2]. The tumor microenvironment is a complex system of hypoxia, low pH and high pressure, composed of tumor cells, stromal cells (including fibroblasts, inflammatory cells, fat cells, glial cells and etc.) and extracellular matrix. Tian et al Cancer Cell Int (2020) 20:512 biological behaviors of tumor cells, including proliferation and metastasis [2, 3]. Tumor cells will present different biological profiles, even functional deficits and tissue specificity [4]
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