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Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway

  • Original Article – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Altered cellular metabolism has received increased attention as an important hallmark of cancer. Activation of FASN has been found to be involved in many human tumors. Despite extensive research in FASN function on cancer, the underlying mechanism is not entirely understood yet.

Methods

Cerulenin was used to suppress the FASN expression in human colorectal cancer cell lines (HT29 and LoVo). Expression of PI3K, Akt, p-Akt, mTOR, p-mTOR, FASN, and AZGP1 was measured using western blotting and qPCR. ATP and lactic acid were assessed to investigate the activation of energy metabolism. Cell cytotoxicity assay was studied by cell counting kit-8 assay. The capacity of cell proliferation and migration was investigated by clonogenic and invasion assay. Analysis of apoptosis and the cell cycle was detected by flow cytometry.

Results

We found that the expression of FASN was down-regulated, while the expression of PI3K, p-Akt, p-mTOR, and AZGP1 was down-regulated in HT29 and LoVo cells treated with FASN inhibitor. Proliferation was reduced in FASN inhibitor-treated cells, which is consistent with an increased apoptosis rate. Furthermore, the migration of FASN inhibitor-treated cells was decreased and the content of ATP and lactic acid was also dropped.

Conclusion

These findings suggest that inhibited FASN suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. The results have paved the way to understand the relations of FASN, mTOR signaling pathway, and energy metabolism in colorectal cancer cells.

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Abbreviations

FASN:

Fatty acid synthase

mTOR:

Mammalian target of rapamycin

PI3K:

Phosphatidylinositol 3-kinase

Akt:

Serine/threonine kinase

ATP:

Adenosine 5′-triphosphate

OXPHOS:

Oxidative phosphorylation

AZGP1:

Zn-alpha-2-glycoprotein 1

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Acknowledgments

This study was supported by the research grants from the National Natural Science Foundation of China (81150028); the Natural Science Foundation of Jiangsu Province, China (BK2012749); Research Fund for the Doctoral Program of Higher Education of China (20120092110065).

Conflict of interest

The authors indicate no potential conflicts of interest.

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    Authors and Affiliations

    1. Department of Internal Medicine, School of Medicine, Southeast University, Nanjing, China

      Ligong Chang, Hui Liu, Xia Shen & Peilin Huang

    2. Department of Pathology, Jiangsu Jiankang Vocational College, Nanjing, China

      Peng Wu

    3. Department of Hematology and Oncology, School of Medicine, Southeast University, Nanjing, China

      Ravichandran Senthilkumar

    4. The Second Affiliated Hospital of Southeast University, Nanjing, China

      Xiaoqiang Tian

    5. Maanshan Municipal People’s Hospital, Maanshan, China

      Zijian Tao

    6. Dingjia Qiao 87, Gulou District, Nanjing, 210009, China

      Peilin Huang

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    1. Ligong Chang
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    Correspondence to Peilin Huang.

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    Ligong Chang and Peng Wu have contributed equally to the work.

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    Chang, L., Wu, P., Senthilkumar, R. et al. Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. J Cancer Res Clin Oncol 142, 59–72 (2016). https://doi.org/10.1007/s00432-015-2000-8

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