Siddharth Sumit, Das Sarita, Nayak Anmada, Kundu Chanakya Nath
Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha, 751024, India.
Clin Exp Metastasis. 2016 Oct;33(7):661-75. doi: 10.1007/s10585-016-9809-7. Epub 2016 Jul 13.
Cancer stem cells drive the metastatic cascade by undergoing epithelial to mesenchymal transition (EMT) and again mesenchymal to epithelial transition (MET). Using multiple breast cancer cell lines including cigarette smoke induced breast cancer cells and tumor derived primary cells from patient sample; we developed a breast cancer metastasis model and reported the existence of an adherent, distinct pre-metastatic phase, quiescent-breast cancer stem cells (Q-BCSCs) prior to attaining an EMT. SURVIVIN was found to be expressed in Q-BCSCs. Time dependant biphasic expression of SURVIVIN in Q-BCSCs reveals that Q-BCSCs is a pre-metastatic phase distinct from both epithelial and mesenchymal counterparts. SURVIVIN favours metastasis and up-regulates WNT/β-CATENIN pathway in a PI3 K/AKT-dependant manner for self-renewal. Knockdown of SURVIVIN in Q-BCSCs lost the metastatic property of cells by inhibiting invasion, EMT-MET, PI3 K/AKT/WNT cascade, and induced apoptosis. Thus, our data suggest the existence of a novel pre-metastatic phase (Q-BCSCs) before EMT and SURVIVIN acts as a marker for Quiescent-BCSCs.
癌症干细胞通过经历上皮-间质转化（EMT）以及再次的间质-上皮转化（MET）来驱动转移级联反应。我们使用多种乳腺癌细胞系，包括香烟烟雾诱导的乳腺癌细胞以及来自患者样本的肿瘤衍生原代细胞，建立了一个乳腺癌转移模型，并报告了在发生EMT之前存在一种贴壁的、独特的转移前静止期乳腺癌干细胞（Q-BCSCs）。研究发现存活素（SURVIVIN）在Q-BCSCs中表达。存活素在Q-BCSCs中的时间依赖性双相表达表明，Q-BCSCs是一个与上皮和间质对应物都不同的转移前阶段。存活素促进转移，并以PI3K/AKT依赖的方式上调WNT/β-连环蛋白通路以实现自我更新。在Q-BCSCs中敲低存活素会通过抑制侵袭、EMT-MET、PI3K/AKT/WNT级联反应而丧失细胞的转移特性，并诱导细胞凋亡。因此，我们的数据表明在EMT之前存在一个新的转移前阶段（Q-BCSCs），且存活素可作为静止期乳腺癌干细胞的标志物。
