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Basal-like breast cancer (BLBC) is associated with a poor clinical outcome as a result of the few treatment options and poor therapeutic response. Here, we report that elevated expression of urine diphosphate-galactose ceramide galactosyltransferase (UGT8) specifically occurs in BLBC and predicts poor prognosis in breast cancer patients. UGT8 expression is transcriptionally up-regulated by Sox10, triggering the sulfatide biosynthetic pathway; increased sulfatide activates integrin αVβ5-mediated signaling that contributes to BLBC progression. UGT8 expression promotes, whereas UGT8 knockdown suppresses tumorigenicity and metastasis. Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which blocks the sulfatide biosynthetic pathway. Significantly, a clinically achievable dosage of ZA exhibits apparent inhibitory effect on migration, invasion, and lung metastasis of BLBC cells. Together, our study suggests that UGT8 is a potential prognostic indicator and druggable target of BLBC and that pharmacologic inhibition of UGT8 by ZA offers a promising opportunity for treating this challenging disease.
Pubmed ID: 29728441
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Project exploring the spectrum of genomic changes involved in more than 20 types of human cancer that provides a platform for researchers to search, download, and analyze data sets generated. As a pilot project it confirmed that an atlas of changes could be created for specific cancer types. It also showed that a national network of research and technology teams working on distinct but related projects could pool the results of their efforts, create an economy of scale and develop an infrastructure for making the data publicly accessible. Its success committed resources to collect and characterize more than 20 additional tumor types. Components of the TCGA Research Network: * Biospecimen Core Resource (BCR); Tissue samples are carefully cataloged, processed, checked for quality and stored, complete with important medical information about the patient. * Genome Characterization Centers (GCCs); Several technologies will be used to analyze genomic changes involved in cancer. The genomic changes that are identified will be further studied by the Genome Sequencing Centers. * Genome Sequencing Centers (GSCs); High-throughput Genome Sequencing Centers will identify the changes in DNA sequences that are associated with specific types of cancer. * Proteome Characterization Centers (PCCs); The centers, a component of NCI's Clinical Proteomic Tumor Analysis Consortium, will ascertain and analyze the total proteomic content of a subset of TCGA samples. * Data Coordinating Center (DCC); The information that is generated by TCGA will be centrally managed at the DCC and entered into the TCGA Data Portal and Cancer Genomics Hub as it becomes available. Centralization of data facilitates data transfer between the network and the research community, and makes data analysis more efficient. The DCC manages the TCGA Data Portal. * Cancer Genomics Hub (CGHub); Lower level sequence data will be deposited into a secure repository. This database stores cancer genome sequences and alignments. * Genome Data Analysis Centers (GDACs) - Immense amounts of data from array and second-generation sequencing technologies must be integrated across thousands of samples. These centers will provide novel informatics tools to the entire research community to facilitate broader use of TCGA data. TCGA is actively developing a network of collaborators who are able to provide samples that are collected retrospectively (tissues that had already been collected and stored) or prospectively (tissues that will be collected in the future).
View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-435 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-436 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BT-20 is a Cancer cell line with a species of origin Homo sapiens (Human)
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