Secretory phospholipase (sPLA2-IIA) regulates breast cancer stem cells differentiation and metastatic potential.

Breast cancer is the second most cancer worldwide in females. The primary factor responsible for tumor recurrence is the presence of breast cancer stem cells (BCSCs), which escape the chemo-radiotherapy. In this study, we have investigated the role of Secretory phospholipase-A2 Group 2A (sPLA 2 -IIA) that is overexpressed in BCSCs of MCF7 and MDA-MB-231 breast cancer cell lines. Further, overexpression of sPLA 2 -IIA revealed an increased EGFR/JNK/c-JUN/c-FOS signaling in BCSCs, while sPLA 2 -IIA knockdown significantly reduced the percentage of BCSCs and decreased signaling in both the cell lines. Importantly, sPLA 2 -IIA knockdown showed differentiation of BCSCs. Strikingly, PET imaging showed a decreased metastatic potential of BCSCs. Our study revealed a novel role of sPLA 2 -IIA in regulating BCSCs, which play a crucial role in regulating the differentiation and metastatic potential of BCSCs. [Display omitted] • SPLA2-IIA knockdown reduces the number of BCSCs. • Loss of sPLA2-IIA decreases the tumorigenic potential of BCSCs in NOD/SCID mice. • SPLA2-IIA knockdown enhances the differentiation potential of BCSCs. • SPLA2-IIA knockdown leads to a decrease in the metastatic potential of BCSCs. • SPLA2-IIA knockdown reduces the EGFR/JNK/c-JUN-c-FOS signaling in BCSCs. [ABSTRACT FROM AUTHOR]