@article{e30673f046d64e0c9b3bd798fe5d0ea3,
title = "Acetyl-CoA Synthetase 2: A Critical Linkage in Obesity-Induced Tumorigenesis in Myeloma",
abstract = "Obesity is often linked to malignancies including multiple myeloma, and the underlying mechanisms remain elusive. Here we showed that acetyl-CoA synthetase 2 (ACSS2) may be an important linker in obesity-related myeloma. ACSS2 is overexpressed in myeloma cells derived from obese patients and contributes to myeloma progression. We identified adipocyte-secreted angiotensin II as a direct cause of adiposity in increased ACSS2 expression. ACSS2 interacts with oncoprotein interferon regulatory factor 4 (IRF4), and enhances IRF4 stability and IRF4-mediated gene transcription through activation of acetylation. The importance of ACSS2 overexpression in myeloma is confirmed by the finding that an inhibitor of ACSS2 reduces myeloma growth both in vitro and in a diet-induced obese mouse model. Our findings demonstrate a key impact for obesity-induced ACSS2 on the progression of myeloma. Given the central role of ACSS2 in many tumors, this mechanism could be important to other obesity-related malignancies.",
keywords = "ACSS2, IRF4, adipocytes, angiotensin II, autophagy, lysine acetylation, multiple myeloma, obesity",
author = "Zongwei Li and Huan Liu and Jin He and Zhiqiang Wang and Zheng Yin and Gichun You and Zhiming Wang and Davis, {Richard E.} and Pei Lin and Bergsagel, {P. Leif} and Manasanch, {Elisabet E.} and Wong, {Stephen T.C.} and Esnaola, {Nestor F.} and Chang, {Jenny C.} and Orlowski, {Robert Z.} and Qing Yi and Jing Yang",
note = "Funding Information: We thank The University of Texas MD Anderson Myeloma Tissue Bank. This research was supported by the National Institutes of Health/National Cancer Institute (R01s: CA190863 and CA193362) and the American Cancer Society (Research Scholar Grant 127337-RSG-15-069-01-TBG). It was also supported by NIH/NCI P30CA016672 for the Small Animal Imaging Facility, Research Histology Core Laboratory, and Flow Cytometry and Cellular Imaging Facility. We thank Ms. Rachael E. Whitehead of Houston Methodist Research Institute for creating the graphical abstract for this manuscript. The CoMMpass datasets were generated as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiatives (https://research.themmrf.org and https://themmrf.org/). Z.L. and J.Y. designed all experiments and wrote the manuscript; Z.L. H.L. J.H. G.Y. and Zhiming Wang performed experiments; Z.Y. and S.T.C.W. performed statistical analysis; P.L. E.E.M. N.F.E. and J.C.C. provided patient samples; Zhiqiang Wang and R.E.D. performed microarray analysis; P.L.B. provided Vk?MYC cells; and R.Z.O. and Q.Y. provided critical suggestions. The authors declare no conflicts of interest. Funding Information: We thank The University of Texas MD Anderson Myeloma Tissue Bank. This research was supported by the National Institutes of Health / National Cancer Institute (R01s: CA190863 and CA193362 ) and the American Cancer Society (Research Scholar Grant 127337-RSG-15-069-01-TBG ). It was also supported by NIH / NCI P30CA016672 for the Small Animal Imaging Facility, Research Histology Core Laboratory, and Flow Cytometry and Cellular Imaging Facility. We thank Ms. Rachael E. Whitehead of Houston Methodist Research Institute for creating the graphical abstract for this manuscript. The CoMMpass datasets were generated as part of the Multiple Myeloma Research Foundation Personalized Medicine Initiatives ( https://research.themmrf.org and https://themmrf.org/ ). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "5",
doi = "10.1016/j.cmet.2020.12.011",
language = "English (US)",
volume = "33",
pages = "78--93.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}