@article{ffb4ef4b83f242f7b5b3a372c11bf00c,
title = "Menin and menin-associated proteins coregulate cancer energy metabolism",
abstract = "The interplay between glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) is central to maintain energy homeostasis. It remains to be determined whether there is a mechanism governing metabolic fluxes based on substrate availability in microenvironments. Here we show that menin is a key transcription factor regulating the expression of OXPHOS and glycolytic genes in cancer cells and primary tumors with poor prognosis. A group of menin-associated proteins (MAPs), including KMT2A, MED12, WAPL, and GATA3, is found to restrain menin{\textquoteright}s full function in this transcription regulation. shRNA knockdowns of menin and MAPs result in reduced ATP production with proportional alterations of cellular energy generated through glycolysis and OXPHOS. When shRNA knockdown cells are exposed to metabolic stress, the dual functionality can clearly be distinguished among these metabolic regulators. A MAP can negatively counteract the regulatory mode of menin for OXPHOS while the same protein positively influences glycolysis. A close-proximity interaction between menin and MAPs allows transcriptional regulation for metabolic adjustment. This coordinate regulation by menin and MAPs is necessary for cells to rapidly adapt to fluctuating microenvironments and to maintain essential metabolic functions.",
keywords = "Circulating tumor cells, Glycolysis, Menin, Menin-associated proteins, Oxidative phosphorylation",
author = "Chou, {Chih Wei} and Xi Tan and Hung, {Chia Nung} and Brandon Lieberman and Meizhen Chen and Meena Kusi and Kohzoh Mitsuya and Lin, {Chun Lin} and Masahiro Morita and Zhijie Liu and Chen, {Chun Liang} and Huang, {Tim Hui Ming}",
note = "Funding Information: Funding: This work was supported by NIH grants U54CA217297 (T.H.-M.H.), Cancer Prevention and Research Institute of Texas (CPRIT) grants RP150600 (T.H.-M.H.) and RR160017 (Z.L.), and the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grant-in-Aid for Scientist Research 18K07237 (M.M.). M.K. was supported by the CPRIT predoctoral training grant RP170345. Funding Information: This work was supported by NIH grants U54CA217297 (T.H.-M.H.), Cancer Prevention and Research Institute of Texas (CPRIT) grants RP150600 (T.H.-M.H.) and RR160017 (Z.L.), and the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grant-in-Aid for Scientist Research 18K07237 (M.M.). M.K. was supported by the CPRIT predoctoral training grant RP170345. We thank the staff of the Bioanalytics and Single-Cell Core (BASiC) and the Next-Generation Sequencing Shared Resource at the University of Texas Health Science Center, San Antonio, and the Proteomics Core at the Sanford-Burnham Prebys Medical Discovery Institute for providing their technical support of genomic, transcriptomic, and proteomic analyses. This work was supported by NIH grants U54CA217297 (T.H.-M.H.) and P30CA054174, Cancer Prevention and Research Institute of Texas (CPRIT) grants RP150600 (T.H.-M.H.) and RR160017 (Z.L.), and the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grant-in-Aid for Scientist Research 18K07237 (M.M.). M.K. was supported by the CPRIT predoctoral training grant RP170345. Funding Information: Acknowledgments: We thank the staff of the Bioanalytics and Single-Cell Core (BASiC) and the Next-Generation Sequencing Shared Resource at the University of Texas Health Science Center, San Antonio, and the Proteomics Core at the Sanford-Burnham Prebys Medical Discovery Institute for providing their technical support of genomic, transcriptomic, and proteomic analyses. This work was supported by NIH grants U54CA217297 (T.H.-M.H.) and P30CA054174, Cancer Prevention and Research Institute of Texas (CPRIT) grants RP150600 (T.H.-M.H.) and RR160017 (Z.L.), and the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) Grant-in-Aid for Scientist Research 18K07237 (M.M.). M.K. was supported by the CPRIT predoctoral training grant RP170345. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2020",
month = sep,
doi = "10.3390/cancers12092715",
language = "English (US)",
volume = "12",
pages = "1--21",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",
}