Growth Factor Receptor in Breast Cancer Progression and Metabolic Regulation

生长因子受体介导的信号通路，如由EGFR和ErbB-2激活的信号通路，在乳腺癌细胞的生长、存活、细胞周期调控、肿瘤启动和肿瘤进展/转移中发挥着积极的作用。此外，越来越多的证据表明，癌症进展和能量代谢之间存在密切关系。新陈代谢失调最近甚至被认为是癌症的第七个标志，此外还有公认的六个标志。开发和利用新的分子疗法需要了解信号异常和代谢调节，以及它们是如何相互联系的。这项更新计划项目拨款(PPG)旨在了解在乳腺肿瘤进展和代谢调节中发挥关键作用的几个关键分子的信号通路。PPG的近期目标是了解EGFR家族介导的信号通路和乳腺癌发生和发展过程中的代谢调节。这个PPG由四个互动项目组成，由一个行政核心提供支持。这四个项目中的每个项目都有自己独特的一套具体目标，以共同主题为目标，并相互依赖于项目组合中其他项目的组成部分。项目1将评估与癌症和代谢调节有关的依赖和非依赖EGFR的途径。项目2计划在转基因小鼠模型中利用EGFR家族在乳腺肿瘤发生和转移中的作用。项目3将研究Rab 25在乳腺癌、生物能量学和自噬中的作用。项目4将研究由14-3-3^引起的代谢失调和乳腺肿瘤的进展/转移。这项PPG的长期目标是了解腹股沟因子受体介导的通路如何促进乳腺癌的进展。除了传统的信号通路外，这一新的PPG还研究了代谢调节如何由生长因子受体调节并参与乳腺癌的进展。这一PPG的结果将促进我们对生长因子受体介导的信号在代谢调节和乳腺癌进展中的作用的理解，并可能为乳腺癌的治疗提供新的方向。

Growth factor receptors-mediated signal pathways, such as those activated by EGFR and ErbB-2, play an active role in breast cancer cell growth, survival, cell cycle deregulation, tumor initiation, and tumor progression/metastasis. Additionally, there is accumulated evidence demonstrating a close relationship between cancer progression and energy metabolism. Metabolic deregulation has even lately been considered as the seventh hallmark of cancers in addition to the well-established six hallmarks. The development and the utilization of novel molecular therapies requires an understanding of both signal aberrations and metabolic regulation, and of how they relate to each other. This renewal program project grant (PPG) aims at understanding signaling pathways of a few key molecules that play critical roles in breast tumor progression and metabolic regulation. The immediate goals of this PPG are to understand the EGFR family-mediated signaling pathways and metabolic regulation in the initiation and progression of breast cancer. This PPG consists of four interactive projects supported by one administrative core. Each of the four projects has its own unique set of specific aims that target at the common theme and are interdependent on components of other projects in the PPG. Project 1 will evaluate pathways of kinase-dependent and -independent of EGFR that link to cancer and metabolic regulation. Project 2 plans to exploit role of EGFR family in mammary tumorigenesis and metastasis in transgenic mice models. Project 3 will examine the role of Rab 25 in breast cancer bioenergetics and autophagy. Project 4 will investigate metabolic deregulation by 14-3-3^ and mammary tumor progression/metastasis. The long-term goals of this PPG are to understand how grovirth factor receptorsmediated pathways may contribute to breast cancer progression. In addition to traditional signal pathways, this renewal PPG also addresses how metabolic regulation may be regulated by growth factor receptors and involved in breast cancer progression. The outcome of this PPG will advance our understanding of the effect of growth factor receptor-mediated signaling on metabolic regulation and breast cancer progression and may shed light on new directions for breast cancer therapy.