Role of Rab1 in Cell Growth and Cancer

描述(由申请人提供)：雷帕霉素的机械性或哺乳动物靶标(MTOR)是细胞生长和增殖的中央控制器，对有丝分裂和营养信号做出反应。MTOR通路在人类癌症中经常被过度激活，导致肿瘤生长失控。因为癌细胞经常对升高的mTOR信号“上瘾”，从而使mTOR成为理想的抗癌药物靶点。高度特异的mTOR抑制剂雷帕霉素类似物(Rapalog)是FDA批准的治疗晚期肾癌和乳腺癌的抗癌药物。然而，由于缺乏对患者对雷帕洛格治疗的反应的了解，它们的疗效受到限制。因此，深入了解mTOR信号转导途径对基础生物学和肿瘤治疗具有重要意义。在这一应用中，我们将研究我们最近发现的一种新的mTOR激活剂Rab1刺激细胞生长和癌症的机制。我们将进一步研究Rab1在乳腺癌病理生物学和靶向治疗中的作用。我们预计，该项目的成功完成将有助于回答一些长期存在的关于细胞调节的问题，并使个体化癌症治疗成为可能。

DESCRIPTION (provided by applicant): Mechanistic or mammalian target of rapamycin (mTOR) is a central controller of cell growth and proliferation in response to mitogenic and nutrient signals. mTOR pathway is frequently hyper-activated in human cancers, leading to uncontrolled cancer growth. Because cancer cells are often 'addicted' to elevated mTOR signaling, rendering mTOR a desirable cancer drug target. The highly specific mTOR inhibitors rapamycin analogs (rapalogs) are FDA-approved anti-cancer drugs for advanced renal and breast cancers. However, their efficacy is limited by lack of understanding of what patients are responsive to rapalog therapy. Therefore, a detailed understanding of mTOR signaling will is of considerable significance to basic biology and cancer therapy. In this application, we will investigate the mechanism of stimulation of cell growth and cancer by Rab1, a novel mTOR activator we recently identified. We will further study the role of Rab1 in the pathobiology and targeted therapy of breast cancer. We anticipate that successful completion of this project will help answer some long-standing questions on cell regulation and enable individualized cancer therapy.