TY - JOUR
T1 - Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
AU - Li, Yanyan
AU - Gong, Di
AU - Zhang, Le
AU - Li, Hongjiang
AU - Zhang, Shu
AU - Zhang, Jie
AU - Li, Kai
AU - Zheng, Qian Wen
AU - Zhao, Gang
AU - Zhang, Yue
AU - Chen, Yue
AU - Guo, Yafei
AU - Xiang, Rong
AU - Lin, Ping
AU - Wei, Yuquan
PY - 2018
Y1 - 2018
N2 - Breast cancer is one of the leading causes of death in women. Due to the existence of a small fraction of stem cell-like subpopulations, some breast cancer subtypes exhibit very high malignancy and resistance to multiple therapies. The underlying mechanisms of how these subtypes acquire stem cell-like properties and progress more aggressively remain largely unknown. Zinc finger protein 32 (ZNF32), a newly discovered transcription factor, has been reported to be associated with breast cancer progression. However, many questions remain about its target genes and its exact mechanisms in regulating stem cell-like properties and drug resistance. In the present study, we examined the relationship between ZNF32 and GPER, a membrane-associated estrogen receptor, and we addressed their roles in stemness regulation in human breast cancer cell lines. Our results showed that ZNF32 could induce expansion of stem cell-like subpopulations and increase drug resistance by upregulating GPER expression, in which ERK activation was also implicated. We also illustrated that ZNF32 induced GPER expression via a ZNF32 binding sequence located within the GPER promoter region. A correlation between ZNF32/GPER expression and increased tumor incidence and burden was observed in xenograft mouse models. We conclude that ZNF32 can engage GPER/ERK signalling and confer breast cancer stem cell-like properties, which may indicate poor prognosis of breast cancer patients. ZNF32 and GPER targeted therapies might provide new solutions for breast cancer treatment.
AB - Breast cancer is one of the leading causes of death in women. Due to the existence of a small fraction of stem cell-like subpopulations, some breast cancer subtypes exhibit very high malignancy and resistance to multiple therapies. The underlying mechanisms of how these subtypes acquire stem cell-like properties and progress more aggressively remain largely unknown. Zinc finger protein 32 (ZNF32), a newly discovered transcription factor, has been reported to be associated with breast cancer progression. However, many questions remain about its target genes and its exact mechanisms in regulating stem cell-like properties and drug resistance. In the present study, we examined the relationship between ZNF32 and GPER, a membrane-associated estrogen receptor, and we addressed their roles in stemness regulation in human breast cancer cell lines. Our results showed that ZNF32 could induce expansion of stem cell-like subpopulations and increase drug resistance by upregulating GPER expression, in which ERK activation was also implicated. We also illustrated that ZNF32 induced GPER expression via a ZNF32 binding sequence located within the GPER promoter region. A correlation between ZNF32/GPER expression and increased tumor incidence and burden was observed in xenograft mouse models. We conclude that ZNF32 can engage GPER/ERK signalling and confer breast cancer stem cell-like properties, which may indicate poor prognosis of breast cancer patients. ZNF32 and GPER targeted therapies might provide new solutions for breast cancer treatment.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85057203017&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30478301
U2 - https://doi.org/10.1038/s41419-018-1144-2
DO - https://doi.org/10.1038/s41419-018-1144-2
M3 - Article
C2 - 30478301
SN - 2041-4889
VL - 9
JO - Cell Death & Disease
JF - Cell Death & Disease
IS - 12
M1 - 1162
ER -