{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:32:04Z","timestamp":1790721124603,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms20123080","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T11:01:57Z","timestamp":1561374117000},"page":"3080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-8852","authenticated-orcid":false,"given":"Fan","family":"Wu","sequence":"first","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"McCuaig","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abel H. Y.","family":"Tan","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshni","family":"Jeelall","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine G.","family":"Bean","sequence":"additional","affiliation":[{"name":"Anatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Dai","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiru","family":"Prasanna","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"},{"name":"Department of Medical Oncology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Batham","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laeeq","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia"},{"name":"ANU Medical School, College of Health and Medicine, The Australian National University, Canberra ACT 0200, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2806-2401","authenticated-orcid":false,"given":"Desmond","family":"Yip","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia"},{"name":"ANU Medical School, College of Health and Medicine, The Australian National University, Canberra ACT 0200, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-693X","authenticated-orcid":false,"given":"Jane E.","family":"Dahlstrom","sequence":"additional","affiliation":[{"name":"Anatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia"},{"name":"ANU Medical School, College of Health and Medicine, The Australian National University, Canberra ACT 0200, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha","family":"Rao","sequence":"additional","affiliation":[{"name":"Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1002\/cncr.27581","article-title":"Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the national comprehensive cancer network","volume":"118","author":"Lin","year":"2012","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1111\/cas.13799","article-title":"Optimizing poly (adp-ribose) polymerase inhibition through combined epigenetic and immunotherapy","volume":"109","author":"Prasanna","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1128\/MCB.01693-13","article-title":"Chromatinized protein kinase c-theta directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells","volume":"34","author":"Zafar","year":"2014","journal-title":"Mol. 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