CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription.

Abstract

Macrophage-capping protein (CAPG) has been shown to promote cancer cell metastasis, although the mechanism remains poorly understood. Methods: Breast cancer (BC) tissue microarray was used to test the role of CAPG in the prognosis of BC patients. Xenograft mice model was used to validate the metastasis promotion role of CAPG in vivo. Gene expression array, chromatin immunoprecipitation and luciferase report assay were performed to search for the target genes of CAPG. Protein immunoprecipitation, MS/MS analysis, tissue microarray and histone methyltransferase assay were used to explore the mechanism of CAPG regulating stanniocalcin 1 (STC-1) transcription. Results: We demonstrate a novel mechanism by which CAPG enhances BC metastasis via promoting the transcription of the pro-metastatic gene STC-1, contributing to increased metastasis in BC. Mechanistically, CAPG competes with the transcriptional repressor arginine methyltransferase 5 (PRMT5) for binding to the STC-1 promoter, leading to reduced histone H4R3 methylation and enhanced STC-1 transcription. Our study also indicates that both CAPG and PRMT5 are independent prognostic factors for BC patient survival. High CAPG level is associated with poor survival, while high PRMT5 expression favors a better prognosis in BC patients. Conclusion: Our findings identify a novel role of CAPG in the promotion of BC metastasis by epigenetically enhancing STC-1 transcription.

• Authors: Sheng Huang, Yayun Chi, Yi Qin, Ziliang Wang, Bingqiu Xiu, Yonghui Su, Rong Guo, Liang Guo, Hefen Sun, Chujia Zeng, Shuling Zhou, Xin Hu, Sheng Liu, Zhimin Shao, Zhaohui Wu, Wei Jin, Jiong Wu
• Journal: Theranostics (Theranostics) Vol. 8 Issue 9 Pg. 2549-2564 ( 2018) ISSN: 1838-7640 [Electronic] Australia
• PMID: 29721098 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• Microfilament Proteins
• Nuclear Proteins
• CAPG protein, human
• teleocalcin
• PRMT5 protein, human
• Protein-Arginine N-Methyltransferases

Topics

• Amino Acid Sequence
• Animals
• Breast Neoplasms (genetics)
• Cell Line, Tumor
• Child, Preschool
• Chromatin Immunoprecipitation (methods)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Glycoproteins (genetics)
• HEK293 Cells
• Heterografts
• Humans
• MCF-7 Cells
• Methylation
• Mice
• Mice, Inbred NOD
• Microfilament Proteins (genetics)
• Nuclear Proteins (genetics)
• Prognosis
• Promoter Regions, Genetic (genetics)
• Protein-Arginine N-Methyltransferases (genetics)
• Transcription, Genetic (genetics)