Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers

Ramon C. Sun; Vikas V. Dukhande; Zhengqiu Zhou; Lyndsay E.A. Young; Shane Emanuelle; Christine Fillmore Brainson; Matthew S. Gentry

doi:10.1016/j.cmet.2019.08.014

Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers

Ramon C. Sun, Vikas V. Dukhande, Zhengqiu Zhou, Lyndsay E.A. Young, Shane Emanuelle, Christine Fillmore Brainson, Matthew S. Gentry

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

54 Scopus citations

Abstract

Nuclear glycogen accumulation has been reported in multiple cancers. Sun et al. show that glycogen is de novo synthesized in the nucleus, and nuclear glycogenolysis provides a carbon pool for histone acetylation. Non-small cell lung cancers suppress nuclear glycogenolysis by down-regulating a key E3 ubiquitin ligase to drive cancer progression.

Original language	English
Pages (from-to)	903-916.e7
Journal	Cell Metabolism
Volume	30
Issue number	5
DOIs	https://doi.org/10.1016/j.cmet.2019.08.014
State	Published - Nov 5 2019

Bibliographical note

Funding Information:
This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G. American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S. and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B. NCI R01 CA237643 to C.F.B. American Association for Cancer Research Innovation and Discovery Grant to C.F.B. and AHA Great Rivers Affiliate Postdoctoral fellowship (12POST12030381) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center, NIH National Center for Advancing Translational Sciences UL1TR001998, the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327, and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558.We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript. Conceptualization, R.C.S. and M.S.G.; Methodology, R.C.S. M.S.G. and C.F.B.; Investigation, R.C.S. V.V.D. S.E. L.E.A.Y. Z.Q.Z. and C.F.B.; Writing – Original Draft, R.C.S. and M.S.G.; Writing – Review & Editing, R.C.S. and M.S.G.; Funding Acquisition, R.C.S. C.F.B. and M.S.G.; Resources, R.C.S. and M.S.G.; Supervision, R.C.S. C.F.B. and M.S.G. The authors declare no competing interests.

Funding Information:
This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G., American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S., and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B., NCI R01 CA237643 to C.F.B., American Association for Cancer Research Innovation and Discovery Grant to C.F.B., and AHA Great Rivers Affiliate Postdoctoral fellowship ( 12POST12030381 ) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center , NIH National Center for Advancing Translational Sciences UL1TR001998 , the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327 , and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558 .We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

E3 ubiquitin ligase
EPM2B
Lafora disease
NHLRC1
glycogen
glycogen phosphorylase
histone acetylation
malin
non-small cell lung cancer
nuclear metabolism

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2019.08.014

Cite this

@article{9c024a2f742048b2947c553d22e9ae43,

title = "Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers",

abstract = "Nuclear glycogen accumulation has been reported in multiple cancers. Sun et al. show that glycogen is de novo synthesized in the nucleus, and nuclear glycogenolysis provides a carbon pool for histone acetylation. Non-small cell lung cancers suppress nuclear glycogenolysis by down-regulating a key E3 ubiquitin ligase to drive cancer progression.",

keywords = "E3 ubiquitin ligase, EPM2B, Lafora disease, NHLRC1, glycogen, glycogen phosphorylase, histone acetylation, malin, non-small cell lung cancer, nuclear metabolism",

author = "Sun, {Ramon C.} and Dukhande, {Vikas V.} and Zhengqiu Zhou and Young, {Lyndsay E.A.} and Shane Emanuelle and Brainson, {Christine Fillmore} and Gentry, {Matthew S.}",

note = "Funding Information: This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G. American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S. and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B. NCI R01 CA237643 to C.F.B. American Association for Cancer Research Innovation and Discovery Grant to C.F.B. and AHA Great Rivers Affiliate Postdoctoral fellowship (12POST12030381) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center, NIH National Center for Advancing Translational Sciences UL1TR001998, the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327, and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558.We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript. Conceptualization, R.C.S. and M.S.G.; Methodology, R.C.S. M.S.G. and C.F.B.; Investigation, R.C.S. V.V.D. S.E. L.E.A.Y. Z.Q.Z. and C.F.B.; Writing – Original Draft, R.C.S. and M.S.G.; Writing – Review & Editing, R.C.S. and M.S.G.; Funding Acquisition, R.C.S. C.F.B. and M.S.G.; Resources, R.C.S. and M.S.G.; Supervision, R.C.S. C.F.B. and M.S.G. The authors declare no competing interests. Funding Information: This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G., American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S., and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B., NCI R01 CA237643 to C.F.B., American Association for Cancer Research Innovation and Discovery Grant to C.F.B., and AHA Great Rivers Affiliate Postdoctoral fellowship ( 12POST12030381 ) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center , NIH National Center for Advancing Translational Sciences UL1TR001998 , the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327 , and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558 .We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

year = "2019",

month = nov,

day = "5",

doi = "10.1016/j.cmet.2019.08.014",

language = "English",

volume = "30",

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T1 - Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers

AU - Sun, Ramon C.

AU - Dukhande, Vikas V.

AU - Zhou, Zhengqiu

AU - Young, Lyndsay E.A.

AU - Emanuelle, Shane

AU - Brainson, Christine Fillmore

AU - Gentry, Matthew S.

N1 - Funding Information: This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G. American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S. and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B. NCI R01 CA237643 to C.F.B. American Association for Cancer Research Innovation and Discovery Grant to C.F.B. and AHA Great Rivers Affiliate Postdoctoral fellowship (12POST12030381) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center, NIH National Center for Advancing Translational Sciences UL1TR001998, the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327, and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558.We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript. Conceptualization, R.C.S. and M.S.G.; Methodology, R.C.S. M.S.G. and C.F.B.; Investigation, R.C.S. V.V.D. S.E. L.E.A.Y. Z.Q.Z. and C.F.B.; Writing – Original Draft, R.C.S. and M.S.G.; Writing – Review & Editing, R.C.S. and M.S.G.; Funding Acquisition, R.C.S. C.F.B. and M.S.G.; Resources, R.C.S. and M.S.G.; Supervision, R.C.S. C.F.B. and M.S.G. The authors declare no competing interests. Funding Information: This study was supported by National Institute of Health (NIH) grants R01 N070899 and P01 NS097197 to M.S.G., American Cancer Society grants in the form of an institutional research grant no. 16-182-28 to R.C.S., and a research scholar grant 133123-RSG-19-081-01-TBG to C.F.B.; NCI K22 CA201036 to C.F.B., NCI R01 CA237643 to C.F.B., American Association for Cancer Research Innovation and Discovery Grant to C.F.B., and AHA Great Rivers Affiliate Postdoctoral fellowship ( 12POST12030381 ) to V.V.D. This research was also supported by funding from the University of Kentucky Markey Cancer Center , NIH National Center for Advancing Translational Sciences UL1TR001998 , the NIH-funded University of Kentucky Center for Cancer and Metabolism P20 GM121327 , and the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center P30CA177558 .We would like to thank Dr. Otto Baba for providing the anti-glycogen antibody, Dr. Craig Vander Kooi and Gentry lab members for vigorous discussions regarding the work, Mrs. Dana Napier and Karrie Jones for performing immunohistochemistry on tissue slices, and the Markey Cancer Center, University of Kentucky for providing human NSCLC tissues that made this study possible. We also would like to thank Dr. Nancy Gough at Bioserendipity for editing this manuscript. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2019/11/5

Y1 - 2019/11/5

N2 - Nuclear glycogen accumulation has been reported in multiple cancers. Sun et al. show that glycogen is de novo synthesized in the nucleus, and nuclear glycogenolysis provides a carbon pool for histone acetylation. Non-small cell lung cancers suppress nuclear glycogenolysis by down-regulating a key E3 ubiquitin ligase to drive cancer progression.

AB - Nuclear glycogen accumulation has been reported in multiple cancers. Sun et al. show that glycogen is de novo synthesized in the nucleus, and nuclear glycogenolysis provides a carbon pool for histone acetylation. Non-small cell lung cancers suppress nuclear glycogenolysis by down-regulating a key E3 ubiquitin ligase to drive cancer progression.

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KW - EPM2B

KW - Lafora disease

KW - NHLRC1

KW - glycogen

KW - glycogen phosphorylase

KW - histone acetylation

KW - malin

KW - non-small cell lung cancer

KW - nuclear metabolism

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Nuclear Glycogenolysis Modulates Histone Acetylation in Human Non-Small Cell Lung Cancers

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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