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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.

SUBMITTER: Rangel R 

PROVIDER: S-EPMC5137755 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.

Rangel Roberto R   Lee Song-Choon SC   Hon-Kim Ban Kenneth K   Guzman-Rojas Liliana L   Mann Michael B MB   Newberg Justin Y JY   Kodama Takahiro T   McNoe Leslie A LA   Selvanesan Luxmanan L   Ward Jerrold M JM   Rust Alistair G AG   Chin Kuan-Yew KY   Black Michael A MA   Jenkins Nancy A NA   Copeland Neal G NG  

Proceedings of the National Academy of Sciences of the United States of America 20161114 48

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 promot  ...[more]

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