دورية أكاديمية
أعرض في EDS

Opioids drive breast cancer metastasis through the δ-opioid receptor and oncogenic STAT3.

التفاصيل البيبلوغرافية
العنوان: Opioids drive breast cancer metastasis through the δ-opioid receptor and oncogenic STAT3.
المؤلفون: Tripolt S; Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria., Neubauer HA; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria., Knab VM; Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria., Elmer DP; Department of Biosciences, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria., Aberger F; Department of Biosciences, Cancer Cluster Salzburg, Paris-Lodron University of Salzburg, Salzburg, Austria., Moriggl R; Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria., Fux DA; Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Vienna, Austria. Electronic address: sabrina_tripolt@gmx.net.
المصدر: Neoplasia (New York, N.Y.) [Neoplasia] 2021 Feb; Vol. 23 (2), pp. 270-279. Date of Electronic Publication: 2021 Jan 16.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 100886622 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5586 (Electronic) Linking ISSN: 14765586 NLM ISO Abbreviation: Neoplasia Subsets: MEDLINE
أسماء مطبوعة: Publication: 2014- : [Amsterdam] : Elsevier
Original Publication: New York, NY : Stockton Press, c1999-
مواضيع طبية MeSH: Analgesics, Opioid/*pharmacology , Breast Neoplasms/*metabolism , Breast Neoplasms/*pathology , Receptors, Opioid, delta/*metabolism , STAT3 Transcription Factor/*metabolism, Animals ; Biomarkers ; Breast Neoplasms/etiology ; Cell Line, Tumor ; Disease Models, Animal ; Disease Susceptibility ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Mice ; Mice, Transgenic ; Neoplasm Metastasis ; Oncogene Proteins/metabolism ; Receptors, Opioid, delta/agonists ; Receptors, Opioid, delta/genetics
مستخلص: The opioid crisis of pain medication bears risks from addiction to cancer progression, but little experimental evidence exists. Expression of δ-opioid receptors (DORs) correlates with poor prognosis for breast cancer patients, but mechanistic insights into oncogenic signaling mechanisms of opioid-triggered cancer progression are lacking. We show that orthotopic transplant models using human or murine breast cancer cells displayed enhanced metastasis upon opioid-induced DOR stimulation. Interestingly, opioid-exposed breast cancer cells showed enhanced migration and strong STAT3 activation, which was efficiently blocked by a DOR-antagonist. Furthermore, opioid treatment resulted in down-regulation of E-Cadherin and increased expression of epithelial-mesenchymal transition markers. Notably, STAT3 knockdown or upstream inhibition through the JAK1/2 kinase inhibitor ruxolitinib prevented opioid-induced breast cancer cell metastasis and migration in vitro and in vivo. We conclude on a novel mechanism whereby opioid-triggered breast cancer metastasis occurs via oncogenic JAK1/2-STAT3 signaling to promote epithelial-mesenchymal transition. These findings emphasize the importance of selective and restricted opioid use, as well as the need for safer pain medication that does not activate these oncogenic pathways.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: I 4157 Austria FWF_ Austrian Science Fund FWF
فهرسة مساهمة: Keywords: Breast cancer; EMT; Metastasis; Opioid; STAT3
المشرفين على المادة: 0 (Analgesics, Opioid)
0 (Biomarkers)
0 (Oncogene Proteins)
0 (Receptors, Opioid, delta)
0 (STAT3 Transcription Factor)
تواريخ الأحداث: Date Created: 20210119 Date Completed: 20211012 Latest Revision: 20230517
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7815495
DOI: 10.1016/j.neo.2020.12.011
PMID: 33465556
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5586
DOI:10.1016/j.neo.2020.12.011