Project description:CSN5 has been implicated as a candidate oncogene in human breast cancers by genetic linkage with activation of the poor-prognosis, wound response gene expression signature. CSN5 is a subunit of the eight-protein COP9 signalosome, a signaling complex with multiple biochemical activities; the mechanism of CSN5 action in cancer development remains poorly understood. Here we show that CSN5 isopeptidase activity is essential for breast epithelial transformation and progression. Amplification of CSN5 is required for transformation of primary human breast epithelial cells by defined oncogenes. The transforming effects of CSN5 require CSN subunits for assembly of the full COP9 signalosome and the isopeptidase activity of CSN5, which potentiates the transcriptional activity of MYC. Transgenic inhibition of CSN5 isopeptidase activity blocks breast cancer progression evoked by MYC and RAS in vivo. These results highlight CSN5 isopeptidase activity in breast cancer progression, suggesting it as a therapeutic target in aggressive human breast cancers. This SuperSeries is composed of the following subset Series: GSE9204: Role of CSN5 in breast cancer (siRNA transfections) GSE9205: Role of CSN5 in breast cancer (array CGH) Refer to individual Series
Project description:PIWI proteins bind to PIWI-interacting RNAs (piRNAs) and play key roles in the biogenesis and functions of piRNAs. It has been reported that PIWI proteins are essential for stem cell self-renewal and germline development in diverse organisms, and are ectopically expressed in multiple forms of cancer. However, the role of PIWI in cancer remains elusive. Here we report that one of the four PIWI proteins in humans, PIWIL4, is highly expressed in both breast cancer tissues and the cytoplasm of MDA-MB-231 cell line derived from breast cancer. Reducing PIWIL4 expression drastically impairs migration ability of MDA-MB-231 cells, significantly increases their apotosis, and mildly affects their proliferation. Our transcriptome and proteome analyses reveal that these functions are at least partially achieved via the PIWIL4 regulation of TGF-beta and FGF signaling pathways and major histocompatibility complex (MHC) class II proteins. These findings suggest that PIWIL4 may serve as a potential therapeutic target for breast cancer.
Project description:Ubiquitin Conjugating Enzyme E2T (UBE2T) expression is elevated in many cancer types including Breast Cancer. Therefore, we analyzed the role of UBE2T in breast cancer. Genetic inhibition of UBE2T expression in breast cancer cell lines resulted in decreased proliferation, and increased cell death.
