Project description:BRMS1L (breast cancer metastasis suppressor 1 likeM-oM-<M-^LBRMS1-like) is a component of the SIN3A-HDAC corepressor complex that suppresses target gene transcription. Here, we show that reduced BRMS1L in breast cancer tissues is associated with tumor metastasis and poor patient survival. Functionally, BRMS1L inhibits migration and invasion of breast cancer cells by inhibiting epithelial-mesenchymal transition (EMT). These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signaling, by facilitating the recruitment of HDAC1 to its promoter and enhancing histone H3K9 deacetylation. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-M-oM-^AM-"-catenin signaling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNAi-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, while ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signaling in breast cancer cells and acts as a breast cancer metastasis suppressor. Ther transfection analysis used here were further desxribed in Chang Gong, eta al.2013. miR-106b expression determines the proliferation paradox of TGF-M-NM-2 in breast cancer cells. Oncogene. 2013 A two chip study using total RNA recovered from MDA-MB-231 breast cancer cells transfected with negative control vector or vector overexpressing BRMS1L for 24 hours. Each chip measures the expression 45033 genes were collected from the authoritative data source including NCBI.
Project description:Although some breast cancer patients die due to tumor metastasis rather than from the primary tumor, the molecular mechanism of metastasis remains unclear. Therefore, it is necessary to inhibit breast cancer metastasis during cancer treatment. In this case, after designing and synthesizing CTI-2, we found that CTI-2 treatment significantly reduced breast cancer cell metastasis in vivo and in vitro. Notably, with the treatment of CTI-2 in breast cancer cells, the expression level of E-cadherin increased, while the expression level of N-cadherin and vimentin decreased. In addition, after CTI-2 treatment, those outflow levels for p-ERK, p-p38, and p-JNK diminished, while no significant changes in the expression levels of ERK, JNK, or p38 were observed. Our conclusion suggested that CTI-2 inhibits the epithelial-mesenchymal transition (EMT) of breast carcinoma cells by inhibiting the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, thereby inhibiting the metastasis of breast tumor cells. Therefore, we believe that CTI-2 is another candidate for breast tumor medication.
Project description:BRMS1L (breast cancer metastasis suppressor 1 like,BRMS1-like) is a component of the SIN3A-HDAC corepressor complex that suppresses target gene transcription. Here, we show that reduced BRMS1L in breast cancer tissues is associated with tumor metastasis and poor patient survival. Functionally, BRMS1L inhibits migration and invasion of breast cancer cells by inhibiting epithelial-mesenchymal transition (EMT). These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signaling, by facilitating the recruitment of HDAC1 to its promoter and enhancing histone H3K9 deacetylation. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10--catenin signaling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNAi-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, while ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signaling in breast cancer cells and acts as a breast cancer metastasis suppressor. Ther transfection analysis used here were further desxribed in Chang Gong, eta al.2013. miR-106b expression determines the proliferation paradox of TGF-β in breast cancer cells. Oncogene. 2013
Project description:Inhibitors of the secretion of cancer exosomes, which promote cancer progression and metastasis, can not only accelerate exosome biology research but also offer therapeutic benefits for cancer patients. We identified sulfisoxazole (SFX) which inhibits exosome secretion from breast cancer cells. SFX, an FDA-approved oral antibiotic, showed significant anti-tumor and anti-metastatic effects in mouse models of breast cancer xenografts, reduced the expression of proteins involved in exosome biogenesis and secretion, and triggered co-localization of multivesicular endosomes (MVEs) with lysosomes for degradation. These findings provide a foundation for exosome-targeted cancer therapies and the mechanistic studies on exosome biology.
Project description:Protein deacetylase SIRT7 is significantly downregulated in lung metastases of human patient and mouse tissues, and predicted metastasis-free survival. To explore the roles of SIRT7 in breast cancer, we analysed the gene expressions in breast cancer BT549 cells with SIRT7 knockdown or not.