title: Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.
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.
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rangel
authors.affiliation: Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.
authors.forename: Song-Choon
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.|Deparment of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 138673.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hon-Kim Ban
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Liliana
authors.initials: L
authors.lastname: Guzman-Rojas
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Mann
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Justin Y
authors.initials: JY
authors.lastname: Newberg
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.
authors.forename: Takahiro
authors.identifier: 0000-0002-6250-1324
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: McNoe
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand.
authors.forename: Luxmanan
authors.initials: L
authors.lastname: Selvanesan
authors.affiliation: Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.
authors.forename: Jerrold M
authors.initials: JM
authors.lastname: Ward
authors.affiliation: Experimental Cancer Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, United Kingdom.
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Rust
authors.affiliation: Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.
authors.forename: Kuan-Yew
authors.initials: KY
authors.lastname: Chin
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Black
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030.|Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.affiliation: Cancer Research Program, Houston Methodist Research Institute, Houston, TX 77030; ncopeland@houstonmethodist.org.|Division of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Biopolis, Singapore 138673.
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000818:Animals; D045744:Cell Line, Tumor; D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D008822:Mice, Transgenic; D016296:Mutagenesis; D020125:Mutation, Missense; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016016:Proportional Hazards Models; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000099169:Fos-Related Antigen 1
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D051059:PTEN Phosphohydrolase; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C108387:TRPS1 protein, human; C487757:Pten protein, mouse
keywords: Sleeping Beauty; TRPS1; breast cancer; metastasis; tumor suppressors