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

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2549-2564
Number of pages16
JournalTheranostics
Volume8
Issue number9
DOIs
StatePublished - Jan 1 2018

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Breast Neoplasms
Neoplasm Metastasis
Proteins
teleocalcin
Tissue Array Analysis
Survival
Chromatin Immunoprecipitation
Luciferases
Immunoprecipitation
Heterografts
Histones
Methylation
Macrophages
Gene Expression
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

Cite this

Huang, S., Chi, Y., Qin, Y., Wang, Z., Xiu, B., Su, Y., ... Wu, J. (2018). CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription. Theranostics, 8(9), 2549-2564. https://doi.org/10.7150/thno.22523

CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription. / Huang, Sheng; Chi, Yayun; Qin, Yi; Wang, Ziliang; Xiu, Bingqiu; Su, Yonghui; Guo, Rong; Guo, Liang; Sun, Hefen; Zeng, Chujia; Zhou, Shuling; Hu, Xin; Liu, Sheng; Shao, Zhimin; Wu, Zhaohui; Jin, Wei; Wu, Jiong.

In: Theranostics, Vol. 8, No. 9, 01.01.2018, p. 2549-2564.

Research output: Contribution to journalArticle

Huang, S, Chi, Y, Qin, Y, Wang, Z, Xiu, B, Su, Y, Guo, R, Guo, L, Sun, H, Zeng, C, Zhou, S, Hu, X, Liu, S, Shao, Z, Wu, Z, Jin, W & Wu, J 2018, 'CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription', Theranostics, vol. 8, no. 9, pp. 2549-2564. https://doi.org/10.7150/thno.22523
Huang, Sheng ; Chi, Yayun ; Qin, Yi ; Wang, Ziliang ; Xiu, Bingqiu ; Su, Yonghui ; Guo, Rong ; Guo, Liang ; Sun, Hefen ; Zeng, Chujia ; Zhou, Shuling ; Hu, Xin ; Liu, Sheng ; Shao, Zhimin ; Wu, Zhaohui ; Jin, Wei ; Wu, Jiong. / CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription. In: Theranostics. 2018 ; Vol. 8, No. 9. pp. 2549-2564.
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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.",
author = "Sheng Huang and Yayun Chi and Yi Qin and Ziliang Wang and Bingqiu Xiu and Yonghui Su and Rong Guo and Liang Guo and Hefen Sun and Chujia Zeng and Shuling Zhou and Xin Hu and Sheng Liu and Zhimin Shao and Zhaohui Wu and Wei Jin and Jiong Wu",
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AU - Wang, Ziliang

AU - Xiu, Bingqiu

AU - Su, Yonghui

AU - Guo, Rong

AU - Guo, Liang

AU - Sun, Hefen

AU - Zeng, Chujia

AU - Zhou, Shuling

AU - Hu, Xin

AU - Liu, Sheng

AU - Shao, Zhimin

AU - Wu, Zhaohui

AU - Jin, Wei

AU - Wu, Jiong

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