文章：

SRC的复兴

A renaissance for SRC

原文发布日期：2004-06-01

DOI: 10.1038/nrc1366

类型: Review Article

开放获取: 否

要点：

1. v-src was the first of numerous viral oncogenes to be identified and is among the best studied of these. The cellular counterpart of this oncogene — c-SRC — is implicated in a range of human cancers.
2. Both overexpression and overactivation of c-SRC can promote the development of cancer. The structural mechanisms by which c-SRC kinase activity is regulated are now well established, and c-SRC is known to have a negative-regulatory domain that is itself regulated through phosphorylation.
3. c-SRC kinase activity is regulated by several mechanisms, including activation by receptor tyrosine kinases and cytoplasmic phosphatases. Levels of c-SRC protein can also be regulated, for example, by targeting this protein for degradation in the ubiquitin–proteasome pathway. In addition, c-SRC function can also be modulated by regulation of its cellular localization.
4. A wide range of c-SRC substrates have been identified, which has led to a better understanding of c-SRC-mediated signal transduction. These substrates include focal-adhesion proteins, adaptor proteins and transcription factors.
5. In addition to cell proliferation, SRC proteins regulate three main cellular functions that ultimately control the behaviour of transformed cells: adhesion, invasion and motility. These functions might also contribute to tumour progression and metastasis.
6. Recently, drug-discovery efforts have led to the development of several c-SRC inhibitors for potential use as anticancer therapeutics.

要点翻译：

1. v-src是首个被鉴定的病毒癌基因，也是其中研究最为深入的一个。该癌基因的细胞对应物——c-SRC——与多种人类癌症相关。
2. c-SRC的过度表达和过度活化均可促进癌症发生。c-SRC激酶活性的结构调控机制目前已明确，已知c-SRC具有一个自身通过磷酸化调控的负性调节结构域。
3. c-SRC激酶活性受多种机制调控，包括受体酪氨酸激酶和细胞质磷酸酶的激活。c-SRC蛋白水平也可通过泛素-蛋白酶体途径靶向降解等方式进行调控。此外，c-SRC功能还可通过其细胞定位的调节来改变。
4. 目前已鉴定出大量c-SRC底物，这使人们对c-SRC介导的信号转导有了更深入的理解。这些底物包括黏着斑蛋白、衔接蛋白和转录因子。
5. 除细胞增殖外，SRC蛋白还调控最终决定转化细胞行为的三个主要细胞功能：黏附、侵袭和运动。这些功能也可能促进肿瘤进展和转移。
6. 近期药物研发工作已促成多种c-SRC抑制剂的开发，这些抑制剂有望成为抗癌治疗药物。

英文摘要：

The c-SRC non-receptor tyrosine kinase is overexpressed and activated in a large number of human malignancies and has been linked to the development of cancer and progression to distant metastases. These observations have led to the recent targeting of c-SRC for the development of anticancer therapeutics, which show promise as a new avenue for cancer treatment. Despite this, however, the precise functions of c-SRC in cancer remain unclear. In addition to increasing cell proliferation, a key role of c-SRC in cancer seems to be to promote invasion and motility, functions that might contribute to tumour progression.

摘要翻译： 

c-SRC非受体酪氨酸激酶在多种人类恶性肿瘤中过表达并激活，与癌症的发生及远处转移密切相关。这些发现促使近期以c-SRC为靶点的抗癌药物研发，展现出癌症治疗新途径的前景。然而，c-SRC在癌症中的确切功能仍不清楚。除促进细胞增殖外，c-SRC在癌症中的关键作用似乎还在于促进侵袭和迁移，这些功能可能有助于肿瘤进展。

原文链接：

A renaissance for SRC