Knockdown of E-cadherin induces cancer stem-cell-like phenotype and drug resistance in cervical cancer cells.

ABSTRACT

Cervical cancer is one of the leading causes of mortality amongst women in developing countries, and resistance to therapy is the main reason for 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, cells with the CSC phenotype were isolated, and we examined the expression levels of stem cell markers and genes associated with epithelial-mesenchymal transition (EMT) using different assays. However, the cells with the CSC phenotype could not be cultured for further cytotoxicity studies, so we established a model of CSC in cervical cancer cells. We performed siRNA-mediated knockdown of E-cadherin in these cells, and studied them for EMT-associated stem-cell-like properties. We also performed dose-dependent cell viability assays using clinically relevant drugs such as cisplatin, cyclopamine, and GANT58 to analyze the drug resistant behavior of these cancer cells. We found that knockdown of E-cadherin induces EMT in cervical cancer cells, imparting stem-cell like characteristics along with enhanced tumorsphere formation, cell migration, invasiveness, and drug resistance. This is the first study to establish a CSC model in cervical cancer cells by knockdown of E-cadherin, which can be used to develop anti-cancer therapies.