MYC, metabolic synthetic lethality, and cancer

Annie L. Hsieh, Chi V. Dang

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The MYC oncogene plays a pivotal role in the development and progression of human cancers. It encodes a transcription factor that has broad reaching effects on many cellular functions, most importantly in driving cell growth through regulation of genes involved in ribosome biogenesis, metabolism, and cell cycle. Upon binding DNA with its partner MAX, MYC recruits factors that release paused RNA polymerases to drive transcription and amplify gene expression. At physiologic levels of MYC, occupancy of high-affinity DNA-binding sites drives ‘house-keeping’ metabolic genes and those involved in ribosome and mitochondrial biogenesis for biomass accumulation. At high oncogenic levels of MYC, invasion of low-affinity sites and enhancer sequences alter the transcriptome and cause metabolic imbalances, which activates stress response and checkpoints such as p53. Loss of checkpoints unleashes MYC’s full oncogenic potential to couple metabolism with neoplastic cell growth and division. Cells that overexpress MYC, however, are vulnerable to metabolic perturbations that provide potential new avenues for cancer therapy.

Original languageEnglish (US)
Title of host publicationRecent Results in Cancer Research
PublisherSpringer New York LLC
Pages73-91
Number of pages19
Volume207
DOIs
StatePublished - 2016
Externally publishedYes

Publication series

NameRecent Results in Cancer Research
Volume207
ISSN (Print)00800015
ISSN (Electronic)21976767

Keywords

  • Cancer therapy
  • Glucose
  • Glutamine
  • Metabolism
  • MYC oncogene
  • Ribosome biogenesis

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'MYC, metabolic synthetic lethality, and cancer'. Together they form a unique fingerprint.

Cite this