1 E-Cadherin knockdown induces cancer stem cell-like phenotype and drug resistance.

Cervical cancer is one of the leading causes of mortality amongst women in developing countries and therapy resistance is the main reason for its treatment failure. Recent advances suggest that cancer stem cells (CSCs) are critically involved in regulating the chemo resistant behavior of cervical cancer cells. In our study the CSC phenotype cells were isolated and the expression of stem cell marker and epithelial-mesenchymal transition (EMT) associated gene was confirmed by various assays. However, these CSC phenotype cells cannot be cultured for further cytotoxicity studies. So, we tried to establish a CSC model in cervical cancer cells. We performed the siRNA-mediated knockdown of E-cadherin (E-cad) in these cells and studied EMT associated stem cell-like properties in them. We also performed dose dependent cell viability assay using clinically relevant drugs such as cisplatin, cyclopamine and GANT58 to analyze the drug resistant behavior of these cancer cells. We found that E-cad knockdown induces EMT in cervical cancer cells imparting stem-cell like characteristics along with enhanced tumorsphere formation, migration, invasion ability and drug resistance. This is the first study to establish a CSC model in cervical cancer cells by knockdown of E-cad which can be utilized for development of anti-cancer therapies.