Mehta Darshan, Roy Sayoni, Joshi Priyanka, Parab Mitali, Waghmare Sanjeev K
Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, Maharashtra, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai, 400085, India.
Stem Cell Biology Group, Waghmare Lab, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai, 410210, Maharashtra, India.
Biochem Biophys Res Commun. 2022 Mar 15;597:102-108. doi: 10.1016/j.bbrc.2022.01.079. Epub 2022 Jan 29.
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, 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 sPLA-IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA-IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA-IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA-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 sPLA-IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells.
乳腺癌干细胞（BCSCs）是一种增殖缓慢的细胞，能够逃避传统的放化疗，从而导致耐药性和复发。尽管已经鉴定出了几种标志物，但开发针对它们的策略仍然具有挑战性。在本研究中，我们使用CD44/CD24标志物从MCF-7细胞系中分离出BCSCs，其在癌症干细胞群体中显示出更高比例的乳腺球。此外，BCSCs的体内致瘤潜力表明，当移植到NOD-SCID小鼠体内时，低至10000个细胞就有形成肿瘤的能力。我们观察到癌症干细胞群体中上皮-间质转化（EMT）标志物水平升高。在癌症干细胞中发现分泌型磷脂酶sPLA-IIA过表达。此外，我们还发现乳腺癌细胞中sPLA-IIA的上调是通过JNK信号介导的，而敲低sPLA-IIA可降低JNK信号、细胞增殖、EMT以及乳腺癌细胞的体内致瘤潜力。我们的研究揭示了sPLA-IIA在两种不同的乳腺癌细胞中过表达，如MCF7（雌激素受体阳性、孕激素受体阳性）和三阴性MDA-MB-231（雌激素受体阴性、孕激素受体阴性、人表皮生长因子受体2阴性）。此外，通过揭示调节乳腺癌细胞增殖和转移的分子机制，发现了sPLA-IIA的新作用。
