Studies On The Synergy Effect Of MRTF-A And STAT3 On Breast Cancer Cell Migration

Breast cancer is the leading cause of cancer death in women worldwide which is closely related to metastasis. Metastasis is a complex pathophysiological process, beginning with the migration and invasion of cancer cells into the surrounding tissues and lymphatics. Cell migration is crucial for many biological processes, including embryonic development, wound healing and immune surveillance, and it also contributes to cell invasion and tumor metastasis. Migration is a complex biological process, which associated with a variety of signaling pathways and transcription factors. Recent datas showed that STAT3 (the signal transducers and activators of transcription 3) and MRTF-A (Myocardin-related transcription factors A) had a significant effect on the migration of breast cancer cells. We want to study whether there is a synergic effect on the migration of breast cancer.First, we used wound healing assay and Transwell experiment to investigate the role in breast cancer cell migration of STAT3 and MRTF-A. The results proved that the MRTF-A and STAT3 can promote the migration of breast cancer cells MCF-7 and MDA-MB-231, and showed obvious synergy.Next, we explored the molecular mechanisms of MRTF-A and STAT3 promoting breast cancer cell migration. First of all, detecte the expression of the migration related gene MYL9 and CYR61 from the promoter transcriptional activity, mRNA level, protein level with luciferase report gene activity assay, RT-PCR, Western Blot. The results showed that MRTF-A and STAT3 can raise the expression of MYL9 and CYR61, and showed obvious synergy. Secondly, we want to determine the relationship between MRTF-A/STAT3 and their Cis-regulatory element CArG box, and the GAS site. Results show that the CArG box plays a very important role in the effect of MRTF-A on the C YR61 and MYL9, GAS site also play an important role in the process. Thirdly, this paper discusses the related signaling pathways during the process that STAT3 and MRTF-A promote the migration of breast cancer cells MCF7 and MDA-MB-231. And it maybe involved in RhoA/ROCK pathway and JAK/STAT3 signaling pathway, then we used the inhibitor of Rho kinases (ROCK), the RhoA effector proteins, to inhibit RhoA/ROCK pathway, and AG490 to inhibit JAK/STAT3 signaling pathway, the expression level of MYL9 and CYR61 was reduced. It indicated that MRTF-A and STAT3 can synergistically permote the migration of breast cancer cells, it provided great significance on mechanism research of breast cancer.