Hallmarks of the cancer cell of origin: Comparisons with "energetic" cancer stem cells (e-CSCs)
Hallmarks of the cancer cell of origin: Comparisons with "energetic" cancer stem cells (e-CSCs)
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DOI：
10.18632/aging.101822
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发表时间：
2019-02-15
期刊：
影响因子：
5.2
通讯作者：
Lisanti, Michael P.
中科院分区：
文献类型：
--
作者：
Sotgia, Federica;Fiorillo, Marco;Lisanti, Michael P.
在这里，我们讨论了癌细胞起源的预期标志，以及这可能与新的肿瘤细胞表型，即“充满活力的”癌症干细胞（e-CSC）有关。e-CSC显示出许多癌细胞起源的特征，包括p21-WAF（CDKN 1A）的过度表达，这是衰老的关键标志物。很容易推测癌细胞起源和e-CSC是密切相关的实体。e-CSC具有杂交表型，共享衰老、“干性”和癌症的关键标志。e-CSC是过度增殖的，并且具有升高的线粒体代谢，具有NRF 2介导的抗氧化反应特征，包括谷氧还蛋白（GLRX）和ALDH 3A 1过表达，这可能与它们逃避衰老有关。最后，在e-CSC中，BCAS 1（乳腺癌扩增序列-1）蛋白表达上调>100倍。BCAS 1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。
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.