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

Roberto Rangel; Song Choon Lee; Kenneth Hon Kim Ban; Liliana Guzman-Rojas; Michael B. Mann; Justin Y. Newberg; Takahiro Kodama; Leslie A. McNoe; Luxmanan Selvanesan; Jerrold M. Ward; Alistair G. Rust; Kuan Yew Chin; Michael A. Black; Nancy A. Jenkins; Neal G. Copeland

doi:10.1073/pnas.1613859113

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

Roberto Rangel, Song Choon Lee, Kenneth Hon Kim Ban, Liliana Guzman-Rojas, Michael B. Mann, Justin Y. Newberg, Takahiro Kodama, Leslie A. McNoe, Luxmanan Selvanesan, Jerrold M. Ward, Alistair G. Rust, Kuan Yew Chin, Michael A. Black, Nancy A. Jenkins, Neal G. Copeland

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49 Scopus citations

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.

Original language	English (US)
Pages (from-to)	E7749-E7758
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	113
Issue number	48
DOIs	https://doi.org/10.1073/pnas.1613859113
State	Published - Nov 29 2016

Keywords

Breast cancer
Metastasis
Sleeping Beauty
TRPS1
Tumor suppressors

ASJC Scopus subject areas

General

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Rangel, R., Lee, S. C., Ban, K. H. K., Guzman-Rojas, L., Mann, M. B., Newberg, J. Y., Kodama, T., McNoe, L. A., Selvanesan, L., Ward, J. M., Rust, A. G., Chin, K. Y., Black, M. A., Jenkins, N. A., & Copeland, N. G. (2016). Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression. Proceedings of the National Academy of Sciences of the United States of America, 113(48), E7749-E7758. https://doi.org/10.1073/pnas.1613859113

Rangel, R, Lee, SC, Ban, KHK, Guzman-Rojas, L, Mann, MB, Newberg, JY, Kodama, T, McNoe, LA, Selvanesan, L, Ward, JM, Rust, AG, Chin, KY, Black, MA, Jenkins, NA & Copeland, NG 2016, 'Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 48, pp. E7749-E7758. https://doi.org/10.1073/pnas.1613859113

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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.",

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AU - Newberg, Justin Y.

AU - Kodama, Takahiro

AU - McNoe, Leslie A.

AU - Selvanesan, Luxmanan

AU - Ward, Jerrold M.

AU - Rust, Alistair G.

AU - Chin, Kuan Yew

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AU - Copeland, Neal G.

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AB - 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.

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

Abstract

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