Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention

Tatsuyuki Chiyoda, Peter C. Hart, Mark A. Eckert, Stephanie M. McGregor, Ricardo R. Lastra, Ryuji Hamamoto, Yusuke Nakamura, S. Diane Yamada, Olufunmilayo I. Olopade, Ernst Lengyel, Iris L. Romero

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6 Citations (Scopus)


Mutations in the breast cancer susceptibility gene 1 (BRCA1) are associated with an increased risk of developing epithelial ovarian cancer. However, beyond the role of BRCA1 in DNA repair, little is known about other mechanisms by which BRCA1 impairment promotes carcinogenesis. Given that altered metabolism is now recognized as important in the initiation and progression of cancer, we asked whether the loss of BRCA1 changes metabolism in the cells of origin of ovarian cancer. The findings show that silencing BRCA1 in ovarian surface epithelial and fallopian tube cells increased glycolysis. Furthermore, when these cells were transfected with plasmids carrying deleterious BRCA1 mutations (5382insC or the P1749R), there was an increase in hexokinase-2 (HK2), a key glycolytic enzyme. This effect was mediated by MYC and the STAT3. To target the metabolic phenotype induced by loss of BRCA1, a drug-repurposing approach was used and aspirin was identified as an agent that counteracted the increase in HK2 and the increase in glycolysis induced by BRCA1 impairment. Evidence from this study indicates that the tumor suppressor functions of BRCA1 extend beyond DNA repair to include metabolic endpoints and identifies aspirin as an ovarian cancer chemopreventive agent capable of reversing the metabolic derangements caused by loss of BRCA1.

Original languageEnglish
Pages (from-to)255-266
Number of pages12
JournalCancer Prevention Research
Issue number4
Publication statusPublished - 2017 Apr 1
Externally publishedYes


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chiyoda, T., Hart, P. C., Eckert, M. A., McGregor, S. M., Lastra, R. R., Hamamoto, R., Nakamura, Y., Yamada, S. D., Olopade, O. I., Lengyel, E., & Romero, I. L. (2017). Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention. Cancer Prevention Research, 10(4), 255-266. https://doi.org/10.1158/1940-6207.CAPR-16-0281