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OCT4B mediates hypoxia-induced cancer dissemination

Oncogene volume 38, pages 1093–1105 (2019)Cite this article

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Abstract

Hypoxia, the reduction of oxygen levels in cells or tissues, elicits a set of genes to adjust physiological and pathological demands during normal development and cancer progression. OCT4, a homeobox transcription factor, is essential for self-renewal of embryonic stem cells, but little is known about the role of OCT4 in non-germ-cell tumorigenesis. Here, we report that hypoxia stimulates a short isoform of OCT4, called OCT4B, via a HIF2α-dependent pathway to induce the epithelial–mesenchymal transition (EMT) and facilitate cancer dissemination. OCT4B overexpression decreased epithelial barrier properties, which led to an increase in cell migration and invasion in lung cancer cells. OCT4B knockdown attenuated HIF2α-induced EMT and inhibited cancer dissemination in cell-line and animal models. We observed that OCT4B bound the SLUG promoter and enhanced its expression, and SLUG silencing inhibited OCT4B-mediated EMT, accompanied with decreased cell migration and invasion. Correlation analysis revealed that OCT4B expression was significantly associated with the SLUG level in lung tumors. These results provide novel insights into OCT4B-mediated oncogenesis in cancer dissemination.

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Acknowledgements

This work was supported by National Tsing Hua University, National Yang-Ming University, Institute of Biomedical Science at Academia Sinica, Ministry of Science and Technology (NSC 102-2320-B-007-010, MOST104-2321-B-010-007, MOST 105–2325-B-010-003, MOST 106-2320-B-007-005-MY3), and Ministry of Health and Welfare (MOHW105-TDU-B-211–134003), Executive Yuan, Taiwan.

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Author notes

  1. These authors contributed equally: Sheng-Chieh Lin, Chi-Hsiu Chung

Authors and Affiliations

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

    Sheng-Chieh Lin, Ming-Han Kuo, Yu-Fan Chiu, Yu-Ting Chou & Cheng-Wen Wu

  2. Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan

    Sheng-Chieh Lin

  3. Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan

    Chi-Hsiu Chung, Chih-Hung Chung & Cheng-Wen Wu

  4. Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan

    Cheng-Han Hsieh & Cheng-Wen Wu

  5. Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan

    Cheng-Han Hsieh

  6. Department of Oral Diagnosis & Pathology, Tri-Service General Hospital, Taipei, Taiwan

    Yi-Shing Shieh

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

    Cheng-Wen Wu

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  1. Sheng-Chieh Lin
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Lin, SC., Chung, CH., Chung, CH. et al. OCT4B mediates hypoxia-induced cancer dissemination. Oncogene 38, 1093–1105 (2019). https://doi.org/10.1038/s41388-018-0487-6

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