Gain of glucose-independent growth upon metastasis of breast cancer cells to the brain Academic Article uri icon

Overview

MeSH Major

  • Brain Neoplasms
  • Breast Neoplasms
  • Glucose

abstract

  • Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients.

publication date

  • February 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4315743

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-14-2268

PubMed ID

  • 25511375

Additional Document Info

start page

  • 554

end page

  • 65

volume

  • 75

number

  • 3