...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cells
【24h】

Cell growth, global phosphotyrosine elevation, and c-Met phosphorylation through Src family kinases in colorectal cancer cells

机译：大肠癌细胞中的细胞生长，全球磷酸酪氨酸升高和通过Src家族激酶的c-Met磷酸化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The heterogeneity of cancer cell signaling is a significant obstacle for the effective development and clinical use of molecularly targeted therapies. As a contribution to a better understanding of the diversity of signaling activities in colorectal cancers (CRCs), we have analyzed the activity of Src family kinases (SFKs), which are implicated in human cancer development, in 64 CRC cell lines. A striking diversity of SFK activity was observed within this panel. Importantly, all CRC lines tested depend on SFK activity for their growth. In addition, SFK activity levels strongly correlated with global levels of tyrosine-phosphorylated (pTyr) proteins in CRC lines. SFK inhibition substantially reduced these pTyr levels, suggesting that SFKs may function as signal integration points and master controllers for the pTyr protein status in CRC lines. The majority of analyzed CRC lines with high-SFK activity express activated c-Met (pYpY1234/1235), a receptor tyrosine kinase contributing to the regulation of cell proliferation, migration, and invasion. Inhibition of SFKs reduced c-Met phosphorylation in most cases, indicating a reversed signal flow from SFK to c-Met. We conclude that SFK activity is important for the growth of CRC lines, although only low activity levels are required. If this also is true for CRC patients, tumors with low-SFK activity may be particularly sensitive to SFK inhibitors, and such patients should be targeted in clinical trials testing SFK inhibitors.
机译：癌细胞信号的异质性是分子靶向疗法有效开发和临床使用的重要障碍。为了更好地理解结直肠癌（CRC）中信号传导活性的多样性，我们在64种CRC细胞系中分析了Src家族激酶（SFK）的活性，这与人类癌症的发展有关。在该小组中观察到了SFK活性的惊人多样性。重要的是，所有测试的CRC系的生长均取决于SFK活性。此外，SFK活性水平与CRC系中酪氨酸磷酸化（pTyr）蛋白的整体水平密切相关。 SFK抑制作用显着降低了这些pTyr水平，表明SFK可能充当CRC系中pTyr蛋白状态的信号整合点和主控制器。分析的大多数具有高SFK活性的CRC系均表达活化的c-Met（pYpY1234 / 1235），这是一种受体酪氨酸激酶，有助于调节细胞增殖，迁移和侵袭。在大多数情况下，抑制SFKs会降低c-Met磷酸化，表明从SFK到c-Met的信号流反向。我们得出结论，尽管仅需要低活性水平，但SFK活性对于CRC系的生长很重要。如果对于CRC患者也是如此，则SFK活性低的肿瘤可能对SFK抑制剂特别敏感，因此应在测试SFK抑制剂的临床试验中将此类患者作为目标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号