KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer

Hunain Alam; Ming Tang; Mayinuer Maitituoheti; Shilpa S. Dhar; Manish Kumar; Chae Young Han; Chandrashekar R. Ambati; Samir B. Amin; Bingnan Gu; Tsai Yu Chen; Yu Hsi Lin; Jichao Chen; Florian L. Muller; Nagireddy Putluri; Elsa R. Flores; Francesco J. DeMayo; Laura Baseler; Kunal Rai; Min Gyu Lee

doi:10.1016/j.ccell.2020.03.005

KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer

Hunain Alam, Ming Tang, Mayinuer Maitituoheti, Shilpa S. Dhar, Manish Kumar, Chae Young Han, Chandrashekar R. Ambati, Samir B. Amin, Bingnan Gu, Tsai Yu Chen, Yu Hsi Lin, Jichao Chen, Florian L. Muller, Nagireddy Putluri, Elsa R. Flores, Francesco J. DeMayo, Laura Baseler, Kunal Rai, Min Gyu Lee

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124 Scopus citations

Abstract

Histone methyltransferase KMT2D is frequently mutated in lung tumors, and Alam et al. identify KMT2D as a lung tumor suppressor. KMT2D deficiency induces aberrant metabolic reprogramming via super-enhancer impairment, conferring sensitivity to glycolytic inhibitors in lung cancer with KMT2D-inactivating mutations.

Original language	English (US)
Pages (from-to)	599-617.e7
Journal	Cancer cell
Volume	37
Issue number	4
DOIs	https://doi.org/10.1016/j.ccell.2020.03.005
State	Published - Apr 13 2020

Keywords

KMT2D
epigenetic modifier
glycolysis
histone methylation
histone methyltransferase
inhibitor
lung cancer
metabolism
super-enhancer
tumor suppressor

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

MD Anderson CCSG core facilities

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Bioinformatics Shared Resource
Genetically Engineered Mouse Facility
Metabolomics Facility
Research Animal Support Facility
Small Animal Imaging Facility
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10.1016/j.ccell.2020.03.005

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Alam, H., Tang, M., Maitituoheti, M., Dhar, S. S., Kumar, M., Han, C. Y., Ambati, C. R., Amin, S. B., Gu, B., Chen, T. Y., Lin, Y. H., Chen, J., Muller, F. L., Putluri, N., Flores, E. R., DeMayo, F. J., Baseler, L., Rai, K., & Lee, M. G. (2020). KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer cell, 37(4), 599-617.e7. https://doi.org/10.1016/j.ccell.2020.03.005

Alam, H, Tang, M, Maitituoheti, M, Dhar, SS, Kumar, M, Han, CY, Ambati, CR, Amin, SB, Gu, B, Chen, TY, Lin, YH, Chen, J, Muller, FL, Putluri, N, Flores, ER, DeMayo, FJ, Baseler, L, Rai, K & Lee, MG 2020, 'KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer', Cancer cell, vol. 37, no. 4, pp. 599-617.e7. https://doi.org/10.1016/j.ccell.2020.03.005

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title = "KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer",

abstract = "Histone methyltransferase KMT2D is frequently mutated in lung tumors, and Alam et al. identify KMT2D as a lung tumor suppressor. KMT2D deficiency induces aberrant metabolic reprogramming via super-enhancer impairment, conferring sensitivity to glycolytic inhibitors in lung cancer with KMT2D-inactivating mutations.",

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author = "Hunain Alam and Ming Tang and Mayinuer Maitituoheti and Dhar, {Shilpa S.} and Manish Kumar and Han, {Chae Young} and Ambati, {Chandrashekar R.} and Amin, {Samir B.} and Bingnan Gu and Chen, {Tsai Yu} and Lin, {Yu Hsi} and Jichao Chen and Muller, {Florian L.} and Nagireddy Putluri and Flores, {Elsa R.} and DeMayo, {Francesco J.} and Laura Baseler and Kunal Rai and Lee, {Min Gyu}",

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doi = "10.1016/j.ccell.2020.03.005",

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AU - Alam, Hunain

AU - Tang, Ming

AU - Maitituoheti, Mayinuer

AU - Dhar, Shilpa S.

AU - Kumar, Manish

AU - Han, Chae Young

AU - Ambati, Chandrashekar R.

AU - Amin, Samir B.

AU - Gu, Bingnan

AU - Chen, Tsai Yu

AU - Lin, Yu Hsi

AU - Chen, Jichao

AU - Muller, Florian L.

AU - Putluri, Nagireddy

AU - Flores, Elsa R.

AU - DeMayo, Francesco J.

AU - Baseler, Laura

AU - Rai, Kunal

AU - Lee, Min Gyu

PY - 2020/4/13

Y1 - 2020/4/13

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AB - Histone methyltransferase KMT2D is frequently mutated in lung tumors, and Alam et al. identify KMT2D as a lung tumor suppressor. KMT2D deficiency induces aberrant metabolic reprogramming via super-enhancer impairment, conferring sensitivity to glycolytic inhibitors in lung cancer with KMT2D-inactivating mutations.

KW - KMT2D

KW - epigenetic modifier

KW - glycolysis

KW - histone methylation

KW - histone methyltransferase

KW - inhibitor

KW - lung cancer

KW - metabolism

KW - super-enhancer

KW - tumor suppressor

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KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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