Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer

Fan Wu, Robert D. McCuaig, Christopher R. Sutton, Abel H.Y. Tan, Yoshni Jeelall, Elaine G. Bean, Jin Dai, Thiru Prasanna, Jacob Batham, Laeeq Malik, Desmond Yip, Jane E. Dahlstrom, Sudha Rao

Research output: Contribution to journalArticle

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Abstract

DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.

Original languageEnglish
Article number3080
Pages (from-to)1-13
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume20
Issue number12
DOIs
Publication statusPublished - Jun 2019

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Triple Negative Breast Neoplasms
Circulating Neoplastic Cells
metastasis
breast
brain
Tumors
Brain
cancer
Neoplasm Metastasis
tumors
Cells
Neoplasms
Breast Neoplasms
Dual-Specificity Phosphatases
Single-Cell Analysis
pleurae
oncogenes
Pleura
Neoplasm Genes
Phosphatases

Cite this

Wu, Fan ; McCuaig, Robert D. ; Sutton, Christopher R. ; Tan, Abel H.Y. ; Jeelall, Yoshni ; Bean, Elaine G. ; Dai, Jin ; Prasanna, Thiru ; Batham, Jacob ; Malik, Laeeq ; Yip, Desmond ; Dahlstrom, Jane E. ; Rao, Sudha. / Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer. In: International Journal of Molecular Sciences. 2019 ; Vol. 20, No. 12. pp. 1-13.
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abstract = "DUSP6 is a dual-specificity phosphatase (DUSP) involved in breast cancer progression, recurrence, and metastasis. DUSP6 is predominantly cytoplasmic in HER2+ primary breast cancer cells, but the expression and subcellular localization of DUSPs, especially DUSP6, in HER2-positive circulating tumor cells (CTCs) is unknown. Here we used the DEPArray system to identify and isolate CTCs from metastatic triple negative breast cancer (TNBC) patients and performed single-cell NanoString analysis to quantify cancer pathway gene expression in HER2-positive and HER2-negative CTC populations. All TNBC patients contained HER2-positive CTCs. HER2-positive CTCs were associated with increased ERK1/ERK2 expression, which are direct DUSP6 targets. DUSP6 protein expression was predominantly nuclear in breast CTCs and the brain metastases but not pleura or lung metastases of TNBC patients. Therefore, nuclear DUSP6 may play a role in the association with cancer spreading in TNBC patients, including brain metastasis.",
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Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer. / Wu, Fan; McCuaig, Robert D.; Sutton, Christopher R.; Tan, Abel H.Y.; Jeelall, Yoshni; Bean, Elaine G.; Dai, Jin; Prasanna, Thiru; Batham, Jacob; Malik, Laeeq; Yip, Desmond; Dahlstrom, Jane E.; Rao, Sudha.

In: International Journal of Molecular Sciences, Vol. 20, No. 12, 3080, 06.2019, p. 1-13.

Research output: Contribution to journalArticle

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AU - Wu, Fan

AU - McCuaig, Robert D.

AU - Sutton, Christopher R.

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AU - Bean, Elaine G.

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AU - Yip, Desmond

AU - Dahlstrom, Jane E.

AU - Rao, Sudha

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