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A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.

ABSTRACT: FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice. Slug mediated FAM3B-258-induced downregulation of adhesion molecules, upregulation of Cdc42, and invasion of colon cancer cells. The expression of FAM3B-258 in human colorectal adenocarcinomas was positively correlated with Slug. These results suggest that FAM3B-258 promotes colon cancer cell invasion and metastasis through upregulation of Slug.

SUBMITTER: Li Z

PROVIDER: S-EPMC7604826 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.

Li Zongmeng Z Mou Haiwei H Wang Ting T Xue Jing J Deng Bo B Qian Lihua L Zhou Ye Y Gong Wanghua W Wang Ji Ming JM Wu Guohao G Zhou Cheng-Fu CF Fang Jing J Le Yingying Y

Cancer letters 20121008 2

FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here we found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3 ...[more]

PMID: 23059759

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Project description: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.

Dataset Information

A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.

Publications

A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expression.

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