文章：

衰老信息分泌组：短信细胞压力

Senescence-messaging secretome: SMS-ing cellular stress

原文发布日期：2009-01-09

DOI: 10.1038/nrc2560

类型: Review Article

开放获取: 否

要点：

1. Cellular senescence is a mechanism that blocks the proliferation of primary, and in some cases premalignant and malignant, cells. It can be activated by a plethora of stress conditions, including oncogene activation, loss of tumour suppressors or critical shortening of telomeres.
2. Oncogene-induced senescence has recently been recognized as a tumour-suppressive mechanism in vivo, in human lesions and in several mouse tumour models.
3. Recent evidence suggests that the induction of senescence requires several secreted factors, including members of Wnt, insulin, transforming growth factor-β, plasmin, interleukin and possibly also interferon signalling cascades. We term these collectively the senescence-messaging secretome (SMS).
4. The SMS and its signalling cascades may converge first at the level of several plasma membrane signalling receptors.
5. The use of secreted factors in senescence could provide a selective advantage to an organism, as it allows for communication between senescent cells and their microenvironment.
6. Counterintuitively, senescent cells may contribute to tumorigenesis by virtue of the SMS, which can cause stromal components to senesce, thereby establishing a pro-mitogenic loop.

要点翻译：

1. 细胞衰老是一种机制，能阻断原代细胞（在某些情况下包括癌前细胞和恶性细胞）的增殖。该机制可被多种应激条件激活，包括癌基因激活、肿瘤抑制因子缺失或端粒严重缩短。
2. 最近在人类病变组织和多种小鼠肿瘤模型研究中发现，癌基因诱导的衰老是一种体内肿瘤抑制机制。
3. 最新证据表明，衰老的诱导需要多种分泌因子参与，包括Wnt信号通路成员、胰岛素、转化生长因子-β、纤溶酶原、白细胞介素以及可能存在的干扰素信号级联。我们将这些因子统称为衰老信息分泌组（SMS）。
4. SMS及其信号级联可能首先在多种质膜信号受体层面实现整合。
5. 利用分泌因子介导衰老过程可为生物体提供选择优势，因为它实现了衰老细胞与微环境之间的信息传递。
6. 与直觉相反的是，衰老细胞可能通过SMS促进肿瘤发生，因为该分泌组能诱导间质成分衰老，从而建立促有丝分裂循环。

英文摘要：

Oncogene-induced cellular senescence constitutes a strong anti-proliferative response, which can be set in motion following either oncogene activation or loss of tumour suppressor signalling. It serves to limit the expansion of early neoplastic cells and as such is a potent cancer-protective response to oncogenic events. Recently emerging evidence points to a crucial role in oncogene-induced cellular senescence for the 'senescence-messaging secretome' or SMS, setting the stage for cross-talk between senescent cells and their environment. How are such signals integrated into a coordinated response and what are the implications of this unexpected finding?

摘要翻译： 

癌基因诱导的细胞衰老构成一种强烈的抗增殖反应，可在癌基因激活或肿瘤抑制信号缺失后启动。其作用是限制早期肿瘤细胞的扩增，因此是一种针对癌基因事件的有效抗癌保护反应。最新出现的证据指出，“衰老信息分泌组”（SMS）在癌基因诱导的细胞衰老中发挥关键作用，为衰老细胞与其环境之间的交流奠定基础。这些信号如何整合为协调反应？这一意外发现又意味着什么？

原文链接：

Senescence-messaging secretome: SMS-ing cellular stress