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TGFβ1 regulates HGF‐induced cell migration and hepatocyte growth factor receptor MET expression via C‐ets‐1 and miR‐128‐3p in basal‐like breast cancer - Breunig - 2018 - Molecular Oncology - Wiley Online Library
TGFB induces cmet through ets1 and mir128-3p

Breast cancer is the most common cancer in women worldwide. The tumor microenvironment contributes to tumor progression by inducing cell dissemination from the primary tumor and metastasis. TGFβ signaling is involved in breast cancer progression and is specifically elevated during metastatic transformation in aggressive breast cancer. In this study, we performed genomewide correlation analysis of TGFBR2 expression in a panel of 51 breast cancer cell lines and identified that MET is coregulated with TGFBR2. This correlation was confirmed at the protein level in breast cancer cell lines and human tumor tissues. Flow cytometric analysis of luminal and basal‐like breast cancer cell lines and examination of 801 tumor specimens from a prospective cohort of breast cancer patients using reverse phase protein arrays revealed that expression of TGFBR2 and MET is increased in basal‐like breast cancer cell lines, as well as in triple‐negative breast cancer tumor tissues, compared to other subtypes. Using real‐time cell analysis technology, we demonstrated that TGFβ1 triggered hepatocyte growth factor (HGF)‐induced and MET‐dependent migration in vitro. Bioinformatic analysis predicted that TGFβ1 induces expression of C‐ets‐1 as a candidate transcription factor regulating MET expression. Indeed, TGFβ1‐induced expression of ETS1 and breast cancer cell migration was blocked by knockdown of ETS1. Further, we identified that MET is a direct target of miR‐128‐3p and that this miRNA is negatively regulated by TGFβ1. Overexpression of miR‐128‐3p reduced MET expression and abrogated HGF‐induced cell migration of invasive breast cancer cells. In conclusion, we have identified that TGFβ1 regulates HGF‐induced and MET‐mediated cell migration, through positive regulation of C‐ets‐1 and negative regulation of miR‐128‐3p expression in basal‐like breast cancer cell lines and in triple‐negative breast cancer tissue.
TGFB  c-met  ets1  HGF 
march 2019 by Segalllab
VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis | Nature Communications
ERK phosphorylation of ETS1 leads to CBP acetylation of ETS1 for increased transcription.


RNAPII pausing and pausing-release is the rate-limiting step for productive transcription of many genes7, 8. Here we show that regulation of RNAPII pause release is critical for angiogenesis, and we delineate a molecular pathway that links VEGF to broad induction of EC gene transcription through RNAPII pause release (Fig. 7d). VEGF activates ERK, which phosphorylates ETS1 at T38 and S41. CBP is recruited to phosphorylated ETS1, inducing acetylation of ETS1 and likely other local chromatin elements such as histones. Acetylated ETS1 recruits BRD4 and the active P-TEFb pause release complex, thereby rapidly and widely increasing gene expression. In addition, VEGF increases ETS1 chromatin occupancy, which contributes to upregulation of late response genes, likely through both increased RNAPII recruitment and pause release (Fig. 7d).
ERK  ets1  acetylation  brd4  cbp  gene_expression 
may 2018 by Segalllab

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acetylation  brd4  c-met  cbp  erk  gene_expression  hgf  tgfb 

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