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

1
Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia
2
Anatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia
3
Department of Medical Oncology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia
4
ANU Medical School, College of Health and Medicine, The Australian National University, Canberra ACT 0200, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(12), 3080; https://doi.org/10.3390/ijms20123080
Received: 30 April 2019 / Revised: 20 June 2019 / Accepted: 22 June 2019 / Published: 24 June 2019
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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. View Full-Text
Keywords: circulating tumor cells (CTCs); DEPArray; dual-specificity phosphatase; HER2; brain metastasis; single cell analysis; triple-negative breast cancer (TNBC) circulating tumor cells (CTCs); DEPArray; dual-specificity phosphatase; HER2; brain metastasis; single cell analysis; triple-negative breast cancer (TNBC)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wu, F.; McCuaig, R.D.; Sutton, C.R.; Tan, A.H.Y.; Jeelall, Y.; Bean, E.G.; Dai, J.; Prasanna, T.; Batham, J.; Malik, L.; Yip, D.; Dahlstrom, J.E.; Rao, S. Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer. Int. J. Mol. Sci. 2019, 20, 3080.

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