G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells

Andrea K. Corbet, Emmanuel Bikorimana, Raya I. Boyd, Doha Shokry, Kelly Kries, Ayush Gupta, Anneliese Paton, Zhengyang Sun, Zeeshan Fazal, Sarah J. Freemantle, Erik R. Nelson, Michael J. Spinella, Ratnakar Singh

Research output: Contribution to journalArticlepeer-review


G0/G1 switch gene 2 (G0S2) is known to inhibit lipolysis by inhibiting adipose triglyceride lipase (ATGL). In this report, we dissect the role of G0S2 in ER+ versus ER- breast cancer. Overexpression of G0S2 in ER- cells increased cell proliferation, while G0S2 overexpression in ER+ cells decreased cell proliferation. Transcriptome analysis revealed that G0S2 mediated distinct but overlapping transcriptional responses in ER- and ER+ cells. G0S2 reduced genes associated with an epithelial phenotype, especially in ER- cells, including CDH1, ELF3, STEAP4 and TACSTD2, suggesting promotion of the epithelial-mesenchymal transition (EMT). G0S2 also repressed estrogen signaling and estrogen receptor target gene signatures, especially in ER+ cells, including TFF1 and TFF3. In addition, G0S2 overexpression increased cell migration in ER- cells and increased estrogen deprivation sensitivity in ER+ cells. Interestingly, two genes downstream of ATGL in fat utilization and very important in steroid hormone biosynthesis, HMGCS1 and HMGCS2, were downregulated in G0S2 overexpressing ER+ cells. In addition, HSD17B11, a gene that converts estradiol to its less estrogenic derivative, estrone, was highly upregulated in G0S2 overexpressing ER+ cells, suggesting G0S2 overexpression has a negative effect on estradiol production and maintenance. High expression of G0S2 and HSD17B11 was associated with improved relapse-free survival in breast cancer patients while high expression of HMGSC1 was associated with poor survival. Finally, we deleted G0S2 in breast cancer-prone MMTV-PyMT mice. Our data indicates a complex role for G0S2 in breast cancer, dependent on ER status, that may be partially mediated by suppression of the estrogen signaling pathway.

Original languageEnglish (US)
Article number101676
JournalTranslational Oncology
StatePublished - Jul 2023


  • Antiestrogen
  • Breast cancer
  • Epithelial mesenchymal transition
  • Estrogen receptor
  • G0S2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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