Consumption of high-fat diet induces tumor progression and epithelial-mesenchymal transition of colorectal cancer in a mouse xenograft model

Feng-Yao Tang, Man-Hui Pai, En-Pei Isabel Chiang
Journal of Nutritional Biochemistry 2012, 23 (10): 1302-13
Epidemiologic studies suggest that intake of high-fat diet (HFD) promotes colon carcinogenesis. Epithelial-mesenchymal transition (EMT) and inflammation play important roles during tumor progression of colorectal cancer (CRC). Oncogenic pathways such as phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR and mitogen-activated protein kinase (MAPK)/ERK signaling cascades induce EMT and inflammation in cancer. No experimental evidence has been demonstrated regarding HFD-mediated tumor progression including EMT in CRC so far. Our results demonstrated that HFD consumption could induce tumor growth and progression, including EMT and inflammation, in a mouse xenograft tumor model. The molecular mechanisms were through activation of MAPK/ERK and PI3K/Akt/mTOR signaling pathways. HFD induced up-regulation of cyclooxygenase-2, cyclin D1 and proliferating cell nuclear antigen proteins concomitant with increases in expression of nuclear factor-κB p65 (RelA) and β-catenin proteins. Surprisingly, HFD consumption could suppress p21(CIP1/WAF1) expression through increases in nuclear histone deacetylase complex (HDAC). Moreover, HFD could mediate the disassembly of E-cadherin adherent complex and the up-regulation of Vimentin and N-cadherin proteins in tumor tissues. Taken together, our novel findings support evidence for HFD-mediated modulation of HDAC activity and activation of oncogenic cascades, which involve EMT and inflammation in CRC, playing important roles in tumor growth and progression in a mouse xenograft model.

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