A novel metabolic function of Myc in regulation of fatty acid synthesis in prostate cancer.

Oncogene
Krishna B SinghShivendra V Singh

Abstract

A subset of human prostate cancer exhibits increased de novo synthesis of fatty acids, but the molecular driver(s) of this metabolic abnormality remains obscure. This study demonstrates a novel metabolic function of c-Myc (Myc) in regulation of fatty acid synthesis. The role of Myc in regulation of fatty acid synthesis was investigated by: (a) interrogation of the prostate cancer The Cancer Genome Atlas (TCGA) dataset, (b) chromatin immunoprecipitation, and (c) determination of the expression of fatty acid synthesis enzymes and targeted metabolomics using a mouse model and human specimens. The expression of MYC was positively associated with that of key fatty acid synthesis genes including ACLY, ACC1, and FASN in prostate cancer TCGA dataset. Chromatin immunoprecipitation revealed Myc occupancy at the promoters of ACLY, ACC1, and FASN. Prostate-specific overexpression of Myc in Hi-Myc transgenic mice resulted in overexpression of ACLY, ACC1, and FASN proteins in neoplastic lesions and increased circulating levels of total free fatty acids. Targeted metabolomics confirmed increased circulating levels of individual fatty acids in the plasma of Hi-Myc mice and human subjects when compared to corresponding controls. Immunohistochem...Continue Reading

References

Jun 24, 1997·Proceedings of the National Academy of Sciences of the United States of America·H ShimC V Dang
Oct 3, 2003·Cancer Cell·Katharine Ellwood-YenCharles L Sawyers
May 10, 2006·Prostate Cancer and Prostatic Diseases·Y Liu
Jun 24, 2008·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Bora GurelAngelo M De Marzo
Mar 26, 2009·Journal of the National Cancer Institute·Toshiro MigitaMassimo Loda
Jun 29, 2010·Cancer Cell·Barry S TaylorWilliam L Gerald
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Aug 24, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark A RubinArul M Chinnaiyan
Apr 17, 2012·Prostaglandins & Other Lipid Mediators·Janel Suburu, Yong Q Chen
Jun 23, 2012·Nature·Catherine S GrassoScott A Tomlins
Apr 10, 2013·Current Drug Targets·Lucy J Schmidt, Donald J Tindall
Oct 18, 2014·Cancer Research·Carmen PrioloMassimo Loda
Sep 19, 2015·Cancer Discovery·Zachary E StineChi V Dang
Mar 19, 2016·Journal of Cellular Biochemistry·Avani R VyasShivendra V Singh
Aug 10, 2019·Molecular Cancer Therapeutics·Krishna B SinghShivendra V Singh
Sep 27, 2019·Carcinogenesis·Krishna B SinghShivendra V Singh
Jan 9, 2020·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

❮ Previous
Next ❯

Citations

Jan 27, 2021·Cancers·Timon A BloedjesJeroen E J Guikema
Jul 3, 2021·International Journal of Molecular Sciences·Jiřina HofmanováJan Vondráček
Jun 20, 2021·Cancer Research·Laura A Sena, Samuel R Denmeade

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE103512

Methods Mentioned

BETA
RNA-Seq
transgenic
immunoprecipitation
ChIP
Hi-Myc
xenograft

Software Mentioned

Aperio ImageScope
ImageJ
GraphPad Prism

Related Concepts

Related Feeds

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

Related Papers

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Bora GurelAngelo M De Marzo
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Andreas PetterssonMassimo Loda
Annual Review of Biochemistry
K B MarcuA J Patel
© 2021 Meta ULC. All rights reserved