| Literature DB >> 34078741 |
Garima Sinha1,2, Alejandra I Ferrer1,2, Seda Ayer2, Markos H El-Far1,2, Sri Harika Pamarthi2, Yahaira Naaldijk2, Pradeep Barak3,4, Oleta A Sandiford2, Bernadette M Bibber1,2, Ghassan Yehia5, Steven J Greco2, Jie-Gen Jiang3,4, Margarette Bryan2, Rakesh Kumar6, Nicholas M Ponzio3,4, Jean-Pierre Etchegaray7, Pranela Rameshwar8,2.
Abstract
The challenge for treating breast cancer (BC) is partly due to long-term dormancy driven by cancer stem cells (CSCs) capable of evading immune response and resist chemotherapy. BC cells show preference for the BM, resulting in poor prognosis. CSCs use connexin 43 (Cx43) to form gap junctional intercellular communication with BM niche cells, fibroblasts, and mesenchymal stem cells (MSCs). However, Cx43 is an unlikely target to reverse BC dormancy because of its role as a hematopoietic regulator. We found N-cadherin (CDH2) and its associated pathways as potential drug targets. CDH2, highly expressed in CSCs, interacts intracellularly with Cx43, colocalizes with Cx43 in BC cells within BM biopsies of patients, and is required for Cx43-mediated gap junctional intercellular communication with BM niche cells. Notably, CDH2 and anti-apoptotic pathways maintained BC dormancy. We thereby propose these pathways as potential pharmacological targets to prevent dormancy and chemosensitize resistant CSCs.Entities:
Year: 2021 PMID： 34078741 PMCID： PMC8200294 DOI： 10.26508/lsa.202000969
Source DB: PubMed Journal: Life Sci Alliance ISSN： 2575-1077