TY - JOUR T1 - Specific N-cadherin–dependent pathways drive human breast cancer dormancy in bone marrow JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000969 VL - 4 IS - 7 SP - e202000969 AU - Garima Sinha AU - Alejandra I Ferrer AU - Seda Ayer AU - Markos H El-Far AU - Sri Harika Pamarthi AU - Yahaira Naaldijk AU - Pradeep Barak AU - Oleta A Sandiford AU - Bernadette M Bibber AU - Ghassan Yehia AU - Steven J Greco AU - Jie-Gen Jiang AU - Margarette Bryan AU - Rakesh Kumar AU - Nicholas M Ponzio AU - Jean-Pierre Etchegaray AU - Pranela Rameshwar Y1 - 2021/07/01 UR - https://www.life-science-alliance.org/content/4/7/e202000969.abstract N2 - 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. ER -