Epigenetic Switch between
                    SOX2
                    and
                    SOX9
                    Regulates Cancer Cell Plasticity

Sheng-Chieh Lin; Yu-Ting Chou; Shih Sheng Jiang; Junn-Liang Chang; Chih-Hung Chung; Yu-Rung Kao; I-Shou Chang; Cheng-Wen Wu

doi:10.1158/0008-5472.can-15-3178

journal article Nov 30, 2016

Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity

Sheng-Chieh Lin Yu-Ting Chou

Shih Sheng Jiang Junn-Liang Chang Chih-Hung Chung

Yu-Rung Kao I-Shou Chang Cheng-Wen Wu

Cancer Research Vol. 76 No. 23 pp. 7036-7048 · American Association for Cancer Research (AACR)

View at Publisher Save 10.1158/0008-5472.can-15-3178

Abstract

Abstract
Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus altering proliferative and invasive capabilities. In lung cancer cells, SOX2 bound the EPCAM promoter to induce EpCAM–p21Cip1–cyclin A2 signaling, encouraging cell proliferation as well as barrier properties. In contrast, SOX9 bound the SLUG promoter to induce SLUG-mediated cell invasion with a spindle-like phenotype. Pharmacologic inhibition of HDAC elevated a SOX9-positive cell population from SOX2-positive cells, whereas ectopic expression of SOX2 inhibited SOX9 with increased H3K9me2 levels on the SOX9 promoter. In clinical specimens, the expression of SOX2 and SOX9 correlated negatively and positively with lung tumor grade, respectively. Our findings identify SOX2 and SOX9 as nodal epigenetic regulators in determining cancer cell plasticity and metastatic progression. Cancer Res; 76(23); 7036–48. ©2016 AACR.

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Citations

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References

Details

Published: Nov 30, 2016
Vol/Issue: 76(23)
Pages: 7036-7048

Authors

S

Sheng-Chieh Lin

1Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

Y

Yu-Ting Chou

1Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.

S

Shih Sheng Jiang

2National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.

J

Junn-Liang Chang

3Department of Pathology and Laboratory Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.; 4Department of Biomedical Engineering, Ming Chuan University, Taoyuan, Taiwan.

C

Chih-Hung Chung

5Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Y

Yu-Rung Kao

5Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

I

I-Shou Chang

2National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.

C

Cheng-Wen Wu

1Institute of Biotechnology, College of Life Science, National Tsing Hua University, Hsinchu, Taiwan.; 5Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.; 6Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.; 7Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.; 8Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.

Funding

Institute of Biomedical Science Award: MOST104-2321-B-010-007 and MOST103-2320-B-007-006-MY3

Cite This Article

Sheng-Chieh Lin, Yu-Ting Chou, Shih Sheng Jiang, et al. (2016). Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity. Cancer Research, 76(23), 7036-7048. https://doi.org/10.1158/0008-5472.can-15-3178

Epigenetic Switch between SOX2 and SOX9 Regulates Cancer Cell Plasticity

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