| Literature DB >> 27849608 |
Roberto Rangel1, Song-Choon Lee2, Kenneth Hon-Kim Ban2,3, Liliana Guzman-Rojas1, Michael B Mann1, Justin Y Newberg1, Takahiro Kodama1, Leslie A McNoe4, Luxmanan Selvanesan4, Jerrold M Ward2, Alistair G Rust5, Kuan-Yew Chin2, Michael A Black4, Nancy A Jenkins1,2, Neal G Copeland6,2.
Abstract
Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1 Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.Entities:
Keywords: Sleeping Beauty; TRPS1; breast cancer; metastasis; tumor suppressors
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Year: 2016 PMID： 27849608 PMCID： PMC5137755 DOI： 10.1073/pnas.1613859113
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205