Background: Cervical cancer is one of the leading causes of cancer related morbidity and mortality amongst women, especially in developing countries. Recent studies suggest that Cancer stem cells (CSC) are critically involved in regulating the chemo resistant behavior of cancer cells and a relapse of the disease. So targeting CSC-like cells along with the bulk tumor cells can be a promising approach for therapeutics. In this context, we demonstrated that knockdown of E-cadherin gene in cervical cancer cells can generate stem cell-like phenotype and induce epithelial to mesenchymal transition. Interestingly, knockdown of E-cadherin gene in normal keratinocytes did not induce CSC-like cells. Methods: In our study the CSC phenotype cells were isolated by side population (SP) assay from cervical cancer cells and immortalized keratinocytes. The expression of stem cell marker and EMT genes were confirmed by qRT-PCR and immunostainings. Further, we performed SiRNA-mediated knockdown of E-Cadherin (E-Cad) and studied the tumorsphere formation, metastasis and invasion ability of cervical cancer cells. Next, using RTPCR based gene expression analysis and tumorsphere formation we studied the stem–like properties of cancer cells. We also performed dose dependent cell viability assay using clinically relevant drugs and inhibitors to analyze the drug resistance behavior of the tumorspheres (cervical organoids). Results: We found that E-Cad knockdown induces EMT in cervical cancer cells with stem cell-like characteristics along with enhanced tumorsphere formation, metastasis and invasion ability. These cells not only possess CSC-like phenotype at transcriptional and translational level but also functionally as shown by drug resistance behavior studies. Conclusion: Thus, we believe that this can be a promising model to study CSC-like characteristics in-vitro in cervical cancer to target the molecular pathways for therapeutics.

Citation Format: Shalmoli Bhattacharyya, Anuka Sharma, Arnab Pal, Radhika Srinivasan. Knockdown of E-cadherin gene in cervical cancer cells: An in vitro model for cancer stem cell phenotype? [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A055. doi:10.1158/1535-7163.TARG-19-A055