Melanie Swan Memorial Translational Centre, Faculty of Sci-Tech, University of Canberra, Bruce ACT 2617, Australia.
Anatomical Pathology, ACT Pathology, The Canberra Hospital, Canberra health Services, Garran ACT 2606, Australia.
Int J Mol Sci. 2019 Jun 24;20(12):3080. doi: 10.3390/ijms20123080.
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.
DUSP6 是一种双特异性磷酸酶（DUSP），参与乳腺癌的进展、复发和转移。在 HER2+原发性乳腺癌细胞中，DUSP6 主要位于细胞质中，但在 HER2 阳性循环肿瘤细胞（CTC）中 DUSP 的表达和亚细胞定位，特别是 DUSP6，尚不清楚。在这里，我们使用 DEPArray 系统从转移性三阴性乳腺癌（TNBC）患者中鉴定和分离 CTC，并进行单细胞 NanoString 分析，以定量 HER2 阳性和 HER2 阴性 CTC 群体中的癌症通路基因表达。所有 TNBC 患者均含有 HER2 阳性 CTC。HER2 阳性 CTC 与 ERK1/ERK2 表达增加相关，而 ERK1/ERK2 是 DUSP6 的直接靶标。在乳腺癌 CTC 和 TNBC 患者的脑转移中，DUSP6 蛋白表达主要位于核内，但在胸膜或肺转移中则不是。因此，核 DUSP6 可能在与 TNBC 患者包括脑转移的癌症扩散的关联中发挥作用。
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