Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.
Roberto RangelSong-Choon LeeKenneth Hon-Kim BanLiliana Guzman-RojasMichael B MannJustin Y NewbergTakahiro KodamaLeslie A McNoeLuxmanan SelvanesanJerrold M WardAlistair G RustKuan-Yew ChinMichael A BlackNancy A JenkinsNeal G CopelandPublished in: Proceedings of the National Academy of Sciences of the United States of America (2016)
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.
Keyphrases
- genome wide
- bioinformatics analysis
- dna methylation
- crispr cas
- genome wide identification
- transcription factor
- epithelial mesenchymal transition
- cell proliferation
- copy number
- gene expression
- type diabetes
- poor prognosis
- induced apoptosis
- oxidative stress
- genome wide analysis
- wild type
- metabolic syndrome
- pi k akt
- skeletal muscle
- cell cycle arrest
- climate change