Nuclear-Biased DUSP6 Expression is Associated with Cancer Spreading Including Brain Metastasis in Triple-Negative Breast Cancer.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Animals
Antineoplastic Agents
/ pharmacology
Antineoplastic Agents, Immunological
/ pharmacology
Biomarkers, Tumor
Brain Neoplasms
/ secondary
Cell Line, Tumor
Cell Nucleus
/ genetics
Disease Models, Animal
Dual Specificity Phosphatase 6
/ antagonists & inhibitors
Female
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
/ drug effects
Histones
/ metabolism
Humans
MAP Kinase Signaling System
Mice
Neoplasm Invasiveness
Neoplasm Staging
Neoplastic Cells, Circulating
/ metabolism
Protein Binding
Protein Transport
Receptor, ErbB-2
/ genetics
Single-Cell Analysis
Triple Negative Breast Neoplasms
/ genetics
Xenograft Model Antitumor Assays
p300-CBP Transcription Factors
/ metabolism
DEPArray
HER2
brain metastasis
circulating tumor cells (CTCs)
dual-specificity phosphatase
single cell analysis
triple-negative breast cancer (TNBC)
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
24 Jun 2019
24 Jun 2019
Historique:
received:
30
04
2019
revised:
20
06
2019
accepted:
22
06
2019
entrez:
27
6
2019
pubmed:
27
6
2019
medline:
18
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31238530
pii: ijms20123080
doi: 10.3390/ijms20123080
pmc: PMC6627630
pii:
doi:
Substances chimiques
ABCB5 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
Antineoplastic Agents
0
Antineoplastic Agents, Immunological
0
Biomarkers, Tumor
0
Histones
0
p300-CBP Transcription Factors
EC 2.3.1.48
p300-CBP-associated factor
EC 2.3.1.48
Receptor, ErbB-2
EC 2.7.10.1
DUSP6 protein, human
EC 3.1.3.48
Dual Specificity Phosphatase 6
EC 3.1.3.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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