Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
Zinc finger protein 32 promotes breast cancer stem cell-like properties through directly promoting GPER transcription
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DOI：
10.1038/s41419-018-1144-2
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Yuquan Wei
中科院分区：
文献类型：
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作者：
Yanyan Li;Di Gong;Le Zhang;Hongjiang Li;Shu Zhang;Jie Zhang;Kai Li;QianWen Zheng;Gang Zhao;Yue Zhang;Yue Chen;Yafei Guo;Rong Xiang;Ping Lin;Yuquan Wei
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.
