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

Autor: Sun QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Ding LW; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. lingwen.dlw@gmail.com., Johnson K; School of Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Zhou S; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Tyner JW; School of Medicine, Oregon Health & Science University, Portland, OR, 97239, USA., Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Doan NB; Department of Pathology and Laboratory Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, 90095, USA., Said JW; Department of Pathology and Laboratory Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA, 90095, USA., Xiao JF; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Loh XY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Ran XB; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Venkatachalam N; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Lao Z; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Chen Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Xu L; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Fan LF; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, 010021, China., Chien W; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA., Lin DC; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA., Koeffler HP; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2019 Aug; Vol. 38 (34), pp. 6196-6210. Date of Electronic Publication: 2019 Jul 22.
DOI: 10.1038/s41388-019-0865-8
Abstrakt: 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.
Databáze: MEDLINE
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