Role of Rab1 in Cell Growth and Cancer

描述（由申请人提供）：机制或哺乳动物雷帕霉素靶点（mTOR）是响应有丝分裂和营养信号的细胞生长和增殖的中心控制器。mTOR通路在人类癌症中经常被过度激活，导致不受控制的癌症生长。因为癌细胞经常对升高的mTOR信号“上瘾”，使mTOR成为理想的癌症药物靶点。高特异性mTOR抑制剂雷帕霉素类似物（rapalogs）是fda批准用于晚期肾癌和乳腺癌的抗癌药物。然而，由于缺乏对哪些患者对rapalog治疗有反应的了解，它们的疗效受到限制。因此，详细了解mTOR信号传导对基础生物学和癌症治疗具有重要意义。在这个应用中，我们将研究Rab1刺激细胞生长和癌症的机制，Rab1是我们最近发现的一种新的mTOR激活剂。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。我们期望这个项目的成功完成将有助于解答一些长期存在的关于细胞调控的问题，并使个体化的癌症治疗成为可能。

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.