Abstract 2341: CAPG improves breast cancer metastasis through competing with PRMT5 to activate STC-1 transcription

Abstract

Abstract Recent studies have shown that over-expression of macrophage-capping protein (CapG)improves cancer cell metastasis. Previously, we demonstrated that CAPG was highly expressed in MDA-MB-231 cell line with high metastatic potency compared with its maternal cell line. Sequencing of CapG-cDNA complex showed some overlap with the sequence of a group of DNA-binding proteins, the basic helix-loop-helix family, including the c-myc oncogene. We supposed that CAPG inhibited cancer cell metastasis through modulating gene transcription as a transcription factor. To examine whether CAPG played a functional role in breast cancer metastasis, three kinds of breast cancer cell lines were applied, including overexpression and knockdown of CAPG. Total RNA from MCF-7 CAPG overexpression cells versus control was obtained. Microarray analysis of global genomic changes was conducted in transcriptional level of these cells. Stanniocalcin 1 (stc-1), an oncogene, was observed significantly up-regulated by over expression of CAPG. Mass spectra and co-immunopreciptation were used to find the potential transcription factors of CAPG. In breast cancer cell lines, we found that CAPG expression is much higher in relatively aggressive cell line than the mild-nature one on both RNA and protein level. CAPG is also higher in cancer tissues than its adjacent noncancerous tissues (ANCT). Furthermore, it was confirmed that CAPG could directly bind to the promoter of stc-1 to activate stc-1 transcription by luciferase report assay and chip experiments. In CAPG overexpression cell line, knock-down of stc-1 could restrain the CAPG-induced migration and invasion. Interestingly, protein arginine methyltransferase 5 (PRMT5) was found as transcription repressor to compete with CAPG in modulating stc-1 transcription. In this study, CAPG was approved to play a direct role in participating transcription for the first time. We also supposed that by combining with PRMT5, CAPG could compete with PRMT5, and prevent PRMT5 from repressing stc-1 transcriptional process. Citation Format: Sheng Huang, Yayun Chi, Jingyan Xue, Zhimin Shao, Zhaohui Wu, Jiong Wu. CAPG improves breast cancer metastasis through competing with PRMT5 to activate STC-1 transcription. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2341. doi:10.1158/1538-7445.AM2014-2341