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The “HER2–PI3K/Akt–FASN Axis” Regulated Malignant Phenotype of Colorectal Cancer Cells

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Lipids

Abstract

Recent evidence suggests that HER2 (ErbB2; Her-2/neu) and the related PI3K/Akt signaling pathway substantially affect the malignant phenotype of colorectal cancer cells. Moreover, fatty acid synthase (FASN), which mediates de-novo fatty acid synthesis, is crucially important in the carcinogenesis process of a variety of cancers, including colorectal cancer. The purpose of this study was to investigate the malignant phenotype regulation of colorectal cancer cells via the “HER2–PI3K/Akt–FASN axis”. Caco-2 cells with high expression of HER2 and FASN and high transfection efficiency were selected for functional characterization. The cells were transfected with either HER2-specific RNAi plasmid or negative control RNAi plasmid, followed by Q-RT-PCR and western blot assays to examine expression of HER2, PI3K, Akt, and FASN. MTT and colony-formation assays were used to assess proliferation. Migration was investigated by use of the transwell assay, and apoptosis and cell cycle were assayed by use of flow cytometry. Expression of HER2, PI3K, Akt, and FASN were downregulated when HER2 was silenced. Proliferation decreased after downregulation of HER2, which was consistent with increased apoptosis. Migration of HER2-silenced cells was also impaired. Loss of HER2 inhibits the activity of the “HER2–PI3K/Akt–FASN axis” of Caco-2 cells, and reduced activity of this axis alters the malignant behavior of Caco-2 cells.

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Abbreviations

FASN:

Fatty acid synthase

Q-RT-PCR:

Quantitative real-time polymerase chain reaction

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

RNAi:

RNA interference

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (30973475) and the Natural Science Foundation of Jiangsu Province, China (BK2008305). Lida Zhang, Xiaojin Yu, Xiaoqiang Tian, Yunlang Cai, Qiqiang Long, and Yinghui Lu also contributed to this study.

Conflict of interest

The authors declare there is no conflict of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Medical School of Southeast University, Dingjia Qiao 87, Nanjing, 210009, People’s Republic of China

    Nan Li, Xiaodong Bu & Peilin Huang

  2. Department of Pathology, Medical School of Southeast University, Nanjing, People’s Republic of China

    Xiaodong Bu, Peng Wu & Peilin Huang

  3. Department of Internal Medicine, The Tumor Hospital of Jiangsu Province, Nanjing, People’s Republic of China

    Pingping Wu

  4. Department of Internal Medicine, The Second Affiliated Hospital of Southeast University, Nanjing, People’s Republic of China

    Peilin Huang

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  1. Nan Li
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  2. Xiaodong Bu
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  3. Peng Wu
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Correspondence to Peilin Huang.

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Li, N., Bu, X., Wu, P. et al. The “HER2–PI3K/Akt–FASN Axis” Regulated Malignant Phenotype of Colorectal Cancer Cells. Lipids 47, 403–411 (2012). https://doi.org/10.1007/s11745-011-3649-7

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  • DOI: https://doi.org/10.1007/s11745-011-3649-7

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