cPLA2 α reversibly regulates different subsets of cancer stem cells transformation in cervical cancer

We provided a model in which cytosolic phospholipase A2 α reversibly regulates the transformation of cervical cancer stem cells from the quiescent epithelial‐like to malignant mesenchymal‐like states by regulating the phosphorylation of PKCζ, which further inhibits β‐catenin‐E‐cadherin interaction in membrane and promotes β‐catenin transl ocation into the nucleus to affect the stem cell phenotype and metastasis in cervical cancer. AbstractCervical cancer stem cells (CCSCs) are considered major causes of chemoresistance/radioresistance and metastasis. Although several cell surface antigens have been identified in CCSCs, these markers vary among tumors because of CSC heterogeneity. However, whether these markers specifically distinguish CCSCs with different functions is unclear. Here, we demonstrated that CCSCs exist in two biologically distinct phenotypes characterized by different levels of cytosolic phospholipase A2 α (cPLA2α) expression. Overexpression of cPLA2α results in a CD44+CD24− phenotype associated with mesenchymal traits, including increased invasive and migration abilities, whereas CCSCs with cPLA2 α downregulation express CD133 and show quiescent epithelial characteristics. In addition, cPLA2α regulates the reversible transition between mesenchymal and epithelial CCSC states through PKCζ, an atypical protein kinase C, which governs cancer cell state changes and the maintenance of various e mbryonic stem cell characteristics, further inhibi...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Cancer Stem Cells Source Type: research