GLI3 and androgen receptor are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells

Min Lin, Haiyan Zhu, Qi Shen, Lu Zhe Sun, Xueqiong Zhu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Hedgehog signaling pathway has been previously elucidated to be inappropriately activated in many human cancers, including ovarian and breast cancer. However, mechanistic contribution of GLI3, one of the terminal effectors of the pathway, to ovarian and mammary cancer development is underexplored. In this study, we investigated whether GLI3 is necessary for the growth and migration of ovarian and breast cancer cells and further explored the underlying mechanism of GLI3-mediated oncogenesis. We report that GLI3 knockdown inhibited growth and migration of androgen receptor (AR)-positive ovarian and breast cancer cells, but not AR-negative ovarian and breast cancer cells. Furthermore, knockdown of AR expression was effective in inhibiting the growth and migration of AR-positive ovarian and breast cancer cells in the presence of GLI3, but not in GLI3 knockdown cells. Similarly, ectopic expression of AR promoted the growth and migration of AR-negative ovarian and breast cancer cells in the presence of GLI3, but not in GLI3 knockdown cells. GLI3 and AR co-immunoprecipitated each other. GLI3 expression was negatively associated with overall survival of ovarian or breast patients whose tumors expressed a high level of AR. Our findings suggest that GLI3 and AR not only physically interact, but also are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells. GLI3-specific inhibitors may be novel therapeutics for AR-expressing ovarian and breast cancers.

Original languageEnglish (US)
Article number110278
JournalCellular Signalling
Volume92
DOIs
StatePublished - Apr 2022

Keywords

  • Androgen receptor
  • Breast cancer
  • GLI3
  • Ovarian cancer
  • Treatment

ASJC Scopus subject areas

  • Cell Biology

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