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

doi:10.1038/s41388-019-0865-8

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

Knight Cancer Institute

Research output: Contribution to journal › Article › peer-review

28 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 language	English (US)
Pages (from-to)	6196-6210
Number of pages	15
Journal	Oncogene
Volume	38
Issue number	34
DOIs	https://doi.org/10.1038/s41388-019-0865-8
State	Published - 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

@article{7113ac5670594c3ebcf420c56b4011eb,

title = "SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells",

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.",

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

note = "Funding Information: 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{\textquoteright}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{\textquoteright}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).",

year = "2019",

month = aug,

day = "22",

doi = "10.1038/s41388-019-0865-8",

language = "English (US)",

volume = "38",

pages = "6196--6210",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "34",

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TY - JOUR

T1 - SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells

AU - Sun, Qiao Yang

AU - Ding, Ling Wen

AU - Johnson, Kara

AU - Zhou, Siqin

AU - Tyner, Jeffrey W.

AU - Yang, Henry

AU - Doan, Ngan B.

AU - Said, Jonathan W.

AU - Xiao, Jin Fen

AU - Loh, Xin Yi

AU - Ran, Xue Bin

AU - Venkatachalam, Nachiyappan

AU - Lao, Zhentang

AU - Chen, Ye

AU - Xu, Liang

AU - Fan, Li Fei

AU - Chien, Wenwen

AU - Lin, De Chen

AU - Koeffler, H. Phillip

N1 - Funding Information: 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).

PY - 2019/8/22

Y1 - 2019/8/22

N2 - 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.

AB - 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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U2 - 10.1038/s41388-019-0865-8

DO - 10.1038/s41388-019-0865-8

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AN - SCOPUS:85070229145

SN - 0950-9232

VL - 38

SP - 6196

EP - 6210

JO - Oncogene

JF - Oncogene

IS - 34

ER -

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

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