OCT4B mediates hypoxia-induced cancer dissemination

Sheng Chieh Lin, Chi Hsiu Chung, Chih Hung Chung, Ming Han Kuo, Cheng Han Hsieh, Yu Fan Chiu, Yi Shing Shieh, Yu Ting Chou*, Cheng-Wen Wu

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)1093-1105
Number of pages13
JournalOncogene
Volume38
Issue number7
DOIs
StatePublished - 14 Feb 2019

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    Lin, S. C., Chung, C. H., Chung, C. H., Kuo, M. H., Hsieh, C. H., Chiu, Y. F., Shieh, Y. S., Chou, Y. T., & Wu, C-W. (2019). OCT4B mediates hypoxia-induced cancer dissemination. Oncogene, 38(7), 1093-1105. https://doi.org/10.1038/s41388-018-0487-6