Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum

The notion that breast cancers can survive in an individual patient in a dormant state only to grow as metastatic disease in the future, is in our view incontrovertibly established. Convincing too is the evidence that surgery to remove the primary tumor often terminates dormancy resulting in acceler...

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Main Authors: Nucharee Yokdang, Iain L.O. Buxton
Format: Article
Language:English
Published: MDPI AG 2011-07-01
Series:Cancers
Subjects:
Online Access:http://www.mdpi.com/2072-6694/3/3/2844/
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author Nucharee Yokdang
Iain L.O. Buxton
author_facet Nucharee Yokdang
Iain L.O. Buxton
author_sort Nucharee Yokdang
collection DOAJ
description The notion that breast cancers can survive in an individual patient in a dormant state only to grow as metastatic disease in the future, is in our view incontrovertibly established. Convincing too is the evidence that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Accepting that many deaths due to breast cancer might be averted were we to understand the cellular mechanisms underlying escape from dormancy, we have examined the extracellular signals produced by breast cancers derived from women with metastatic breast disease. In this perspective, we explore the role of extracellular nucleotide signaling that we have proposed constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. A role for the dinucleotide kinase NM23/NDPK (nucleoside diphosphate kinase) secreted by breast tumor cells in the generation of signals that stimulate vascular leakiness, anti-thrombosis, endothelial migration and growth, constitutes a mechanistic basis for escape from latency and offers putative therapeutic targets for breast cancer management not previously appreciated.
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spelling doaj.art-0f3e2594de11498a87adf26f2ecd51812023-08-02T00:35:27ZengMDPI AGCancers2072-66942011-07-01332844285710.3390/cancers3032844Extracellular NM23 Signaling in Breast Cancer: Incommodus VerumNucharee YokdangIain L.O. BuxtonThe notion that breast cancers can survive in an individual patient in a dormant state only to grow as metastatic disease in the future, is in our view incontrovertibly established. Convincing too is the evidence that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. Accepting that many deaths due to breast cancer might be averted were we to understand the cellular mechanisms underlying escape from dormancy, we have examined the extracellular signals produced by breast cancers derived from women with metastatic breast disease. In this perspective, we explore the role of extracellular nucleotide signaling that we have proposed constitutes a pathological axis from the transformed tumor cell to the endothelium in the service of intravasation, dissemination, extravasation and angiogenesis. A role for the dinucleotide kinase NM23/NDPK (nucleoside diphosphate kinase) secreted by breast tumor cells in the generation of signals that stimulate vascular leakiness, anti-thrombosis, endothelial migration and growth, constitutes a mechanistic basis for escape from latency and offers putative therapeutic targets for breast cancer management not previously appreciated.http://www.mdpi.com/2072-6694/3/3/2844/breast cancerdormancylatencyNDPKnucleotidespurinergic receptorssignalingangiogenesis
spellingShingle Nucharee Yokdang
Iain L.O. Buxton
Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
Cancers
breast cancer
dormancy
latency
NDPK
nucleotides
purinergic receptors
signaling
angiogenesis
title Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
title_full Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
title_fullStr Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
title_full_unstemmed Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
title_short Extracellular NM23 Signaling in Breast Cancer: Incommodus Verum
title_sort extracellular nm23 signaling in breast cancer incommodus verum
topic breast cancer
dormancy
latency
NDPK
nucleotides
purinergic receptors
signaling
angiogenesis
url http://www.mdpi.com/2072-6694/3/3/2844/
work_keys_str_mv AT nuchareeyokdang extracellularnm23signalinginbreastcancerincommodusverum
AT iainlobuxton extracellularnm23signalinginbreastcancerincommodusverum