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

Qiao Yang Sun, Ling Wen Ding, Kara Johnson, Siqin Zhou, Jeffrey W. Tyner, Henry Yang, Ngan B. Doan, Jonathan W. Said, Jin Fen Xiao, Xin Yi Loh, Xue Bin Ran, Nachiyappan Venkatachalam, Zhentang Lao, Ye Chen, Liang Xu, Li Fei Fan, Wenwen Chien, De Chen Lin, H. Phillip Koeffler

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6196-6210
Number of pages15
JournalOncogene
Volume38
Issue number34
DOIs
StatePublished - Aug 22 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Sun, Q. Y., Ding, L. W., Johnson, K., Zhou, S., Tyner, J. W., Yang, H., Doan, N. B., Said, J. W., Xiao, J. F., Loh, X. Y., Ran, X. B., Venkatachalam, N., Lao, Z., Chen, Y., Xu, L., Fan, L. F., Chien, W., Lin, D. C., & Koeffler, H. P. (2019). SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells. Oncogene, 38(34), 6196-6210. https://doi.org/10.1038/s41388-019-0865-8