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Gewählte Publikation:

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Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2021

AutorInnen: Tripolt, S; Neubauer, HA; Knab, VM; Elmer, DP; Aberger, F; Moriggl, R; Fux, DA

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

Quelle: Neoplasia. 2021; 23(2):270-279



Autor/innen der Vetmeduni Vienna:

Fux Daniela
Knab Vanessa-Maria
Moriggl Richard
Neubauer Heidi
Tripolt Sabrina

Beteiligte Vetmed-Organisationseinheiten
Institut für Tierzucht und Genetik, Abteilung für Funktionelle Krebsgenomik
Institut für Pharmakologie und Toxikologie, Abteilung für Klinische Pharmakologie


Zugehörige(s) Projekt(e): Stat1onieren Irf1 in Mammakarzinogenese und Therapie


Abstract:
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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