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SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

Oncogene volume 38, pages 6196–6210 (2019)Cite this article

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Abstract

Apoptosis of cancer cells occurs by a complex gene regulatory network. Here we showed that SOX7 was significantly downregulated in different cancer types, especially in lung and breast cancers. Low expression of SOX7 was associated with advantage stage of cancer with shorter overall survival. Cancer cells with loss of SOX7 promoted cell survival and colony formation, suppressed cellular apoptosis and produced a drug resistant phenotype against a variety of chemo/targeting therapeutic agents. Mechanistically, SOX7 induced cellular apoptosis through upregulation of genes associated with both P38 and apoptotic signaling pathway, as well as preventing the proteasome mediated degradation of pro-apoptotic protein BIM. Treatment of either a proteasome inhibitor MG132 or bortezomib, or with a p-ERK/MEK inhibitor U0126 attenuate the SOX7 promoted BIM degradation. We identified Panobinostat, an FDA approved pan-HDAC inhibitor, could elevate and restore SOX7 expression in SOX7 silenced lung cancer cells. Taken together, these data revealed an unappreciated role of SOX7 in regulation of cellular apoptosis through control of MAPK/ERK-BIM signaling.

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Acknowledgements

Research was supported by the National Research Foundation Singapore under the Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/0021/2014) and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), the NMRC Centre Grant awarded to National University Cancer Institute of Singapore, the National Research Foundation Singapore, the Singapore Ministry of Education under its Research Centers of Excellence initiatives and RNA Biology Center at the Cancer Science Institute of Singapore (NUS, as part of funding under the Singapore Ministry of Education’s Tier 3 grants, grant number MOE2014-T3–1–006). This research was also supported by the Tower Cancer Research Foundation Michele and Ted Kaplan Family Senior Investigator Grant and Department of Defense USAMRMC (Proposal Number BM160010, Award Number W81XWH-17–1–0093).

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Authors and Affiliations

  1. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Qiao-Yang Sun, Ling-Wen Ding, Siqin Zhou, Henry Yang, Jin-Fen Xiao, Xin-Yi Loh, Xue-Bin Ran, Nachiyappan Venkatachalam, Zhentang Lao, Ye Chen, Liang Xu, Li-Fei Fan & H. Phillip Koeffler

  2. School of Medicine, Oregon Health & Science University, Portland, OR, 97239, USA

    Kara Johnson & Jeffrey W. Tyner

  3. Department of Pathology and Laboratory Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, 90095, USA

    Ngan B. Doan & Jonathan W. Said

  4. School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, 010021, China

    Li-Fei Fan

  5. Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA

    Wenwen Chien, De-Chen Lin & H. Phillip Koeffler

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Sun, QY., Ding, LW., Johnson, K. et al. SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells. Oncogene 38, 6196–6210 (2019). https://doi.org/10.1038/s41388-019-0865-8

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