| Literature DB >> 29743594 |
Aditya Parekh1, Subhayan Das1, Sheetal Parida1, Chandan Kanta Das1, Debabrata Dutta2, Sanjaya K Mallick3, Pei-Hsun Wu4, B N Prashanth Kumar1, Rashmi Bharti1, Goutam Dey1, Kacoli Banerjee1, Shashi Rajput1, Deblina Bharadwaj1, Ipsita Pal1, Kaushik Kumar Dey1, Yetirajam Rajesh1, Bikash Chandra Jena1, Angana Biswas1, Payel Banik1, Anjan K Pradhan5, Swadesh K Das5, Amit Kumar Das2, Santanu Dhara1, Paul B Fisher5, Denis Wirtz4, Gordon B Mills6, Mahitosh Mandal7.
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.Entities:
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Year: 2018 PMID： 29743594 DOI： 10.1038/s41388-018-0272-6
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867