期刊
CELL COMMUNICATION AND SIGNALING
卷 17, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s12964-019-0348-0
关键词
Breast cancer; PC4; Warburg effect; C-Myc; Metastasis; Proliferation
类别
资金
- National Key Research and Development Program [2016YFC1000805]
- Natural Science Foundation Programs [81372727, 81773352]
- University Innovation Team Building Program of Chongqing [CXTDG201602020]
Background: The human positive cofactor 4 (PC4) is initially identified as a transcriptional cofactor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of PC4 in breast cancer development and progression are still unknown. Methods: We investigated PC4 expression in 114 cases of primary breast cancer and matched normal breast tissue specimens, and studied the impact of PC4 expression as well as the molecular mechanisms of this altered expression on breast cancer growth and metastasis both in vitro and in vivo. Results: PC4 was significantly upregulated in breast cancer and high PC4 expression was positively correlated with metastasis and poor prognosis of patients. Gene set enrichment analysis (GSEA) demonstrated that the gene sets of cell proliferation and Epithelial-Mesenchymal Transition (EMT) were positively correlated with elevated PC4 expression. Consistently, loss of PC4 markedly inhibited the growth and metastasis of breast cancer both in vitro and in vivo. Mechanistically, PC4 exerted its oncogenic functions by directly binding to c-Myc promoters and inducing Warburg effect. Conclusions: Our study reveals for the first time that PC4 promotes breast cancer progression by directly regulating c-Myc transcription to promote Warburg effect, implying a novel therapeutic target for breast cancer.
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