School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong SAR.
School of Life Sciences, The Chinese University of Hong Kong, Hong Kong SAR.
Neoplasia. 2018 Mar;20(3):295-303. doi: 10.1016/j.neo.2018.01.005. Epub 2018 Feb 22.
It has long been a puzzle in cancer treatment that despite the initial appearance of apoptosis, the process could be reversed in some cancer cells and often results in more aggressive tumors and metastasis. The mechanism for this recurrence is yet unknown. Here we report that human mammary carcinoma cells induced to undergo apoptosis could recover with increased tumorigenicity in vitro and in vivo, and induced lymph node metastasis. Specifically, the reversed cells underwent epithelial-to-mesenchymal transitions in the primary tumors in situ, and mesenchymal-to-epithelial transitions in the metastatic cells. Flow cytometry confirmed an elevated percentage of cells carrying cancer stem cells (CSCs) markers (CD44/CD24) in the reversed breast cancer cell population, with hypomethylated CD44 promoters and hypermethylated CD24 promoters. More importantly, CSCs were generated anew from non-stem cancer cells after apoptosis reversal possibly through epigenetic modifications. The results from this study can open doors to discovering more effective cancer treatments by suppressing apoptosis reversal.
长期以来，癌症治疗一直存在一个难题，即尽管最初出现了细胞凋亡，但在某些癌细胞中，这个过程可能会被逆转，而且往往会导致肿瘤更具侵袭性和转移。目前尚不清楚这种复发的机制。在这里，我们报告说，诱导人乳腺癌细胞发生凋亡后，它们在体外和体内的致瘤性会恢复，并诱导淋巴结转移。具体来说，逆转的细胞在原位原发性肿瘤中经历上皮间质转化，而在转移性细胞中经历间质上皮转化。流式细胞术证实，逆转的乳腺癌细胞群体中携带癌症干细胞 (CSC) 标志物（CD44/CD24）的细胞比例升高，CD44 启动子低甲基化，CD24 启动子高甲基化。更重要的是，CSC 可能是通过表观遗传修饰从非干细胞性癌细胞中新产生的。这项研究的结果为通过抑制细胞凋亡逆转来发现更有效的癌症治疗方法开辟了道路。
