AI Article Synopsis
- There is a significant link between multinucleated cells (MNCs) and resistance to chemotherapy in various cancers, but more research is needed to fully understand how MNCs influence the tumor environment.
- MNCs from triple-negative breast cancer have been found to alter their micro-environment without proliferating, leading to the secretion of factors like VEGF and MIF that promote chemo-resistance.
- The study highlights the role of reactive oxygen species (ROS) and the HIF-1α signaling pathway in MNCs, suggesting that targeting this pathway might help overcome drug resistance in breast cancer.
Article Abstract
Although there is a strong correlation between multinucleated cells (MNCs) and cancer chemo-resistance in variety of cancers, our understanding of how multinucleated cells modulate the tumor micro-environment is limited. We captured multinucleated cells from triple-negative chemo-resistant breast cancers cells in a time frame, where they do not proliferate but rather significantly regulate their micro-environment. We show that oxidatively stressed MNCs induce chemo-resistance in vitro and in vivo by secreting VEGF and MIF. These factors act through the RAS/MAPK pathway to induce chemo-resistance by upregulating anti-apoptotic proteins. In MNCs, elevated reactive oxygen species (ROS) stabilizes HIF-1α contributing to increase production of VEGF and MIF. Together the data indicate, that the ROS-HIF-1α signaling axis is very crucial in regulation of chemo-resistance by MNCs. Targeting ROS-HIF-1α in future may help to abrogate drug resistance in breast cancer.
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| http://dx.doi.org/10.1038/s41388-018-0272-6 | DOI Listing |
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