Secretory phospholipase sPLA₂-IIAloss impairs tumorigenic and metastatic potential in breast cancer cells

Breast cancer stem cells (BCSCs) are slow cycling cells that escape the traditional chemo-radio-therapy, thereby contributing in resistance and recurrence. Although several markers have been identified, it is still challenging to develop strategies targeting them. In this study, we have isolated BCSCs from MCF-7 cell line using markers CD44⁺/CD24^-/low, which showed higher percentage of mammospheres in CSC population. Moreover, in vivo tumorigenic potential of BCSCs showed as low as 10,000 cells had the ability to develop tumors when transplanted into NOD-SCID mice. We observed an increased level of EMT markers in CSC population. Overexpression of secretory phospholipase sPLA₂-IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA₂-IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA₂-IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA₂-IIA in two different breast cancer cells such as MCF7 (ER+,PR+) and a triple negative, MDA-MB-231 (ER-PR-HER2-). Further, the novel role of sPLA₂-IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells.