Stem-cell driven cancer "Hands-off" regulation of cancer development
Stem-cell driven cancer "Hands-off" regulation of cancer development
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DOI：
10.4161/cc.8.9.8217
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发表时间：
2009-05-01
期刊：
影响因子：
4.3
通讯作者：
Sanchez-Garcia, Isidro
中科院分区：
文献类型：
--
作者：
Vicente-Duenas, Carolina;Perez-Caro, Maria;Sanchez-Garcia, Isidro
一种癌症教条认为，癌基因的失活可以导致癌症缓解，这意味着癌基因是癌症的致命弱点。这种目前的“动手”癌症模型将癌基因作为治疗靶点，并与人类癌症中所有癌细胞携带相同的致癌遗传病变这一事实相一致，这些癌细胞与肿瘤内存在的细胞异质性无关。现在，在一项研究BCR-ABL癌基因在癌症发展中的作用的研究中，这一规则被打破了，在小鼠模型中，癌基因的表达仅限于干细胞区室。BCR-ABL与人类慢性髓性白血病（chronic myeloid leukemia， CML）疾病有关，本研究表明，通过限制癌基因在Sca1（+）细胞中的表达，可引起CML，这表明维持癌基因的表达对于分化肿瘤细胞的产生并不重要，并显示出BCR-ABL在调节癌症形成方面的“不干预”作用。在这里，我们提供了该系统用于人类癌症建模的最新进展，以及它在癌症干细胞（CSCs）的治疗靶向和癌基因的不干涉功能方面的潜在应用。
A cancer dogma states that inactivation of oncogene(s) can cause cancer remission, implying that oncogenes are the Achilles' heel of cancers. This current "hands on" model of cancer has kept oncogenes firmly in focus as therapeutic targets and is in agreement with the fact that in human cancers all cancerous cells, with independence of the cellular heterogeneity existing within the tumor, carry the same oncogenic genetic lesions. This rule has now been broken in a study of the effect of the BCR-ABL oncogene in cancer development in a mouse model in which oncogene expression is restricted to the stem cell compartment. BCR-ABL is linked to chronic myeloid leukemia (CML) disease in humans, and this study shows that by limiting the oncogene expression to Sca1(+) cells CML arises, indicating that maintenance of oncogene expression is not critical for the generation of differentiated tumor cells and showing a "hands off" role for BCR-ABL in regulating cancer formation. Here we provide an update on the use of this system for modeling human cancer and its potential application for therapeutic targeting of cancer stem cells (CSCs) and the hands-off function of oncogenes.