Sotgia Federica, Fiorillo Marco, Lisanti Michael P
Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre (BRC), University of Salford, Greater Manchester, M5 4WT, United Kingdom.
The Department of Pharmacy, Health and Nutritional Sciences, The University of Calabria, Cosenza, Italy.
Aging (Albany NY). 2019 Feb 13;11(3):1065-1068. doi: 10.18632/aging.101822.
Here, we discuss the expected hallmark(s) of the cancer cell of origin and how this may be related to a new tumor cell phenotype, namely "energetic" cancer stem cells (e-CSCs). e-CSCs show many features that would be characteristic of the cancer cell of origin, including the over-expression of p21-WAF (CDKN1A), a key marker of senescence. It is tempting to speculate that the cancer cell of origin and e-CSCs are closely related entities. e-CSCs possess a hybrid phenotype, sharing key hallmarks of senescence, "stemness" and cancer. e-CSCs are hyper-proliferative and have elevated mitochondrial metabolism, with an NRF2-mediated anti-oxidant response signature, including glutaredoxin (GLRX) and ALDH3A1 over-expression, possibly related to their escape from senescence. Finally, in e-CSCs, BCAS1 (Breast carcinoma-amplified sequence-1) protein expression was up-regulated by >100-fold. BCAS1 is a candidate oncogene associated with "stemness" and aggressive oncogenic behavior, such as Tamoxifen resistance.
在此，我们讨论起源癌细胞的预期特征，以及这如何与一种新的肿瘤细胞表型相关，即“能量型”癌症干细胞（e-CSCs）。e-CSCs表现出许多起源癌细胞的特征，包括衰老的关键标志物p21-WAF（CDKN1A）的过表达。很容易推测起源癌细胞和e-CSCs是密切相关的实体。e-CSCs具有混合表型，兼具衰老、“干性”和癌症的关键特征。e-CSCs增殖过度，线粒体代谢增强，具有NRF2介导的抗氧化反应特征，包括谷氧还蛋白（GLRX）和ALDH3A1的过表达，这可能与它们从衰老中逃逸有关。最后，在e-CSCs中，BCAS1（乳腺癌扩增序列-1）蛋白表达上调超过100倍。BCAS1是一种与“干性”和侵袭性致癌行为（如他莫昔芬耐药）相关的候选癌基因。
