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Elevated lipogenesis in epithelial stem-like cell confers survival advantage in ductal carcinoma in situ of breast cancer

Oncogene volume 32, pages 5111–5122 (2013)Cite this article

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Abstract

Upregulation of lipogenesis is a hallmark of cancer and blocking the lipogenic pathway is known to cause tumor cell death by apoptosis. However, the exact role of lipogenesis in tumor initiation is as yet poorly understood. We examined the expression profile of key lipogenic genes in clinical samples of ductal carcinoma in situ (DCIS) of breast cancer and found that these genes were significantly upregulated in DCIS. We also isolated cancer stem-like cells (CSCs) from DCIS.com cell line using cell surface markers (CS24−CD44+ESA+) and found that this cell population has significantly higher tumor-initiating ability to generate DCIS compared with the non-stem-like population. Furthermore, the CSCs showed significantly higher level of expression of all lipogenic genes than the counterpart population from non-tumorigenic breast cancer cell line, MCF10A. Importantly, ectopic expression of SREBP1, the master regulator of lipogenic genes, in MCF10A significantly enhanced lipogenesis in stem-like cells and promoted cell growth as well as mammosphere formation. Moreover, SREBP1 expression significantly increased the ability of cell survival of CSCs from MCF10AT, another cell line that is capable of generating DCIS, in mouse and in cell culture. These results indicate that upregulation of lipogenesis is a pre-requisite for DCIS formation by endowing the ability of cell survival. We have also shown that resveratrol was capable of blocking the lipogenic gene expression in CSCs and significantly suppressed their ability to generate DCIS in animals, which provides us with a strong rationale to use this agent for chemoprevention against DCIS.

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Acknowledgements

This work was supported by the National Institutes of Health (Grants R01CA124650, R01CA129000 and R01CA124650-04S1 to KW), the US Department of Defense (BC096982 to KW) and McElroy Foundation (to KW).

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Authors and Affiliations

  1. Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA

    P R Pandey, F Xing, S Sharma, M Watabe, S K Pai, M Iiizumi-Gairani, K Fukuda & K Watabe

  2. Department of Gastroenterology and Hepatology, School of Medicine, Iwate Medical University, Morioka City, Japan

    S Hirota

  3. Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA

    F Xing, Y-Y Mo & K Watabe

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  1. P R Pandey
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Correspondence to K Watabe.

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Pandey, P., Xing, F., Sharma, S. et al. Elevated lipogenesis in epithelial stem-like cell confers survival advantage in ductal carcinoma in situ of breast cancer. Oncogene 32, 5111–5122 (2013). https://doi.org/10.1038/onc.2012.519

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