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Theranostics 2018; 8(9):2549-2564. doi:10.7150/thno.22523 This issue Cite

Research Paper

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

Sheng Huang^1,2#, Yayun Chi^1,#, Yi Qin^3,#, Ziliang Wang⁴, Bingqiu Xiu¹, Yonghui Su¹, Rong Guo¹, Liang Guo¹, Hefen Sun¹, Chujia Zeng¹, Shuling Zhou⁵, Xin Hu¹, Sheng Liu⁶, Zhimin Shao¹, Zhaohui Wu⁷, Wei Jin^1,✉, Jiong Wu^1,✉

1. Department of Breast Surgery, Breast Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
2. The Second Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), Kunming, Yunnan, People's Republic of China
3. Department of Pancreas & Hepatobiliary Surgery, Pancreas & Hepatobiliary Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
4. Cancer Institute, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
5. Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China
6. Department of Breast Surgery and Pharmacology Laboratory of Traditional Chinese Medicine, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
7. Department of Pathology and Laboratory Medicine; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, Tennessee
^# These authors contributed equally to this work.

✉ Corresponding author: Jiong Wu, Department of Breast Surgery, Building 2, No. 270 Dong An Road, Shanghai, 200032 Email: wujiong1122sina.com; Tel: 86-21-64175590-3423; Fax: 86-21-64172585 or Wei Jin, Breast Cancer Institute, Building 7, No. 270 Dong An Road, Shanghai, 200032 Email: jinwei7207com; Tel: 86-21-64175590-3423; Fax: 86-21-64172585; More

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.

Keywords: breast cancer, metastasis, CAPG, PRMT5, STC-1

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