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Review
. 2020 Apr;38(4):487-503.
doi: 10.1002/stem.3157. Epub 2020 Feb 26.

cPLA2α reversibly regulates different subsets of cancer stem cells transformation in cervical cancer

Yuchao He  1 , Manyu Xiao  1 , Hui Fu  2 , Lu Chen  3   4 , Lisha Qi  4   5 , Dongming Liu  4   5 , Piao Guo  1 , Liwei Chen  1 , Yi Luo  1 , Huiting Xiao  6 , Ning Zhang  1   7 , Hua Guo  1
Affiliations
Review

cPLA2α reversibly regulates different subsets of cancer stem cells transformation in cervical cancer

Yuchao He et al. Stem Cells. 2020 Apr.

Abstract

Cervical 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 A2α (cPLA2α) expression. Overexpression of cPLA2α results in a CD44+ CD24- phenotype associated with mesenchymal traits, including increased invasive and migration abilities, whereas CCSCs with cPLA2α 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 embryonic stem cell characteristics, further inhibiting β-catenin-E-cadherin interaction in membrane and promoting β-catenin translocation into the nucleus to affect the transcriptional regulation of stemness signals. We propose that reversible transitions between mesenchymal and epithelial CCSC states regulated by cPLA2α are necessary for cervical cancer metastasis and recurrence. Thus, cPLA2α might be an attractive therapeutic target for eradicating different states of CCSCs to eliminate tumors more effectively.

Keywords: CD133; CD24; CD44; cPLA2α; cancer stem cells; epithelial-mesenchymal transition.

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References

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