Characterization of novel markers of senescence and their prognostic potential in cancer.
Characterization of novel markers of senescence and their prognostic potential in cancer.
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DOI：
10.1038/cddis.2014.489
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发表时间：
2014-11-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
细胞衰老是一种终末分化状态，已被提出在肿瘤抑制和衰老中起作用。这一观点得到了以下事实的支持，即可以观察到衰老细胞的积累是对致癌应激的反应，也是正常生物体衰老的结果。因此，在体内和体外识别衰老细胞具有重要的诊断和治疗潜力。参与触发和/或维持衰老表型的分子途径尚未完全了解。因此，目前用于检测衰老细胞的标志物是有限的，缺乏特异性。为了解决这一问题，我们筛选了优先在衰老细胞中表达的质膜相关蛋白。我们鉴定了107个可能是衰老的潜在标志物的蛋白质，并验证了其中的10个（DEP 1，NTAL，EBP 50，STX 4，VAMP 3，ARMX 3，B2 MG，LANCL 1，VPS 26 A和PLD 3）。我们证明了这些蛋白质的组合可用于特异性识别培养物和组织样品中的衰老细胞，并且我们使用其中两种（DEP 1和B2 MG）开发了一种简单的基于荧光激活细胞分选的检测方法。值得注意的是，我们发现这些标志物中的几种的表达与不同肿瘤中的存活率增加相关，特别是在乳腺癌中。因此，我们的研究结果可以促进衰老的研究，确定潜在的新的效应器和这种细胞机制的调节剂，并提供潜在的诊断和预后工具，用于临床。
Cellular senescence is a terminal differentiation state that has been proposed to have a role in both tumour suppression and ageing. This view is supported by the fact that accumulation of senescent cells can be observed in response to oncogenic stress as well as a result of normal organismal ageing. Thus, identifying senescent cells in in vivo and in vitro has an important diagnostic and therapeutic potential. The molecular pathways involved in triggering and/or maintaining the senescent phenotype are not fully understood. As a consequence, the markers currently utilized to detect senescent cells are limited and lack specificity. In order to address this issue, we screened for plasma membrane-associated proteins that are preferentially expressed in senescent cells. We identified 107 proteins that could be potential markers of senescence and validated 10 of them (DEP1, NTAL, EBP50, STX4, VAMP3, ARMX3, B2MG, LANCL1, VPS26A and PLD3). We demonstrated that a combination of these proteins can be used to specifically recognize senescent cells in culture and in tissue samples and we developed a straightforward fluorescence-activated cell sorting-based detection approach using two of them (DEP1 and B2MG). Of note, we found that expression of several of these markers correlated with increased survival in different tumours, especially in breast cancer. Thus, our results could facilitate the study of senescence, define potential new effectors and modulators of this cellular mechanism and provide potential diagnostic and prognostic tools to be used clinically.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
78.5
作者：
Collado, Manuel;Serrano, Manuel
通讯作者：
Serrano, Manuel
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars