Growth Factor Receptor in Breast Cancer Progression and Metabolic Regulation

生长因子受体介导的信号通路，例如由EGFR和ErbB-2激活的那些，在乳腺癌细胞生长、存活、细胞周期失调、肿瘤起始和肿瘤进展/转移中发挥积极作用。此外，越来越多的证据表明癌症进展与能量代谢之间存在密切关系。代谢失调甚至最近被认为是癌症的第七个标志，除了公认的六个标志。开发和利用新的分子疗法需要了解信号畸变和代谢调节，以及它们如何相互关联。该更新计划项目资助（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一些关键分子的信号通路。本PPG的直接目标是了解乳腺癌发生和进展中EGFR家族介导的信号通路和代谢调控。这一方案编制补助金包括由一个行政核心支助的四个互动项目。这四个项目中的每一个都有其独特的一套具体目标，这些目标针对共同的主题，并与项目编制补助金中其他项目的组成部分相互依存。项目1将评估与癌症和代谢调节相关的EGFR激酶依赖性和非依赖性途径。项目2计划在转基因小鼠模型中探索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14-3-3^代谢失调和乳腺肿瘤进展/转移。PPG的长期目标是了解生长因子受体介导的通路如何促进乳腺癌进展。除了传统的信号通路外，这种更新PPG还解决了代谢调节如何受到生长因子受体的调节并参与乳腺癌进展。PPG的结果将促进我们对生长因子受体介导的信号传导对代谢调节和乳腺癌进展的影响的理解，并可能为乳腺癌治疗提供新的方向。

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.