The Hippo Tumor Suppressor Network: From Organ Size Control to Stem Cells and Can

河马肿瘤抑制网络：从器官大小控制到干细胞和罐头

• 批准号: 8528306
• 负责人: DAVID L. WOODLAND
• 金额: $ 0.4万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528306
• 关键词: Adherens Junction; Affect; Antineoplastic Agents; Architecture; Biology; California; Cancer Etiology; Cell Polarity; Cell membrane; Cellular Structures; Clinical; Clinical Oncology; Collaborations; Communities; Complex; Data; Development; Discipline; Drosophila genus; Event; Genetic; Industry; Lead; Learning; Lesion; Malignant Neoplasms; Mammalian Cell; Mammals; Membrane; Mission; Molecular; Network-based; Oncogenes; Organ Size; Outcome; Participant; Pathway interactions; Regulation; Research; Research Personnel; Signal Transduction; Stem Cell Factor; Stem Cell Research; Stem cells; Structure; TAZ gene; Therapeutic; Therapeutic Intervention; Tight Junctions; Tumor Suppressor Proteins; Work; base; cancer cell; cancer stem cell; cancer therapy; fly; gene function; inhibitor/antagonist; interest; meetings; public health relevance; receptor; small molecule; stem cell biology; stemness; symposium

DESCRIPTION (provided by applicant): Support is requested for a Keystone Symposia meeting entitled The Hippo Tumor Suppressor Network: From Organ Size Control to Stem Cells and Cancer, organized by Marius Sudol, Helen McNeill, Georg A. Halder and Giovanni Blandino. The meeting will be held in Monterey, California from May 19 - 23, 2013. The general topic of this meeting is relevant to the NCI mission with respect to research into the development of new cancer therapies. Moreover, most of the speakers invited to speak at the symposium are basic cancer researchers who have been supported by NCI. Over the past several years, the Hippo tumor suppressor pathway has emerged as a complex signaling network that has significant implications for our understanding of the molecular mechanisms of cancer development and stem cell biology. The main effectors of this pathway, YAP and TAZ, are transcriptional co- activators, which act as stemness factors and potent oncogenes. Recent studies have revealed that abnormal expression of components of the network can lead to cancer. Therefore, the pathway and its networking molecules are attractive targets for the development of cancer drugs and unconventional therapeutic interventions. Several paradoxes have emerged in the field in recent years, and fast progress in this field is due, in large part, t an active dialog between Drosophila geneticists and mammalian signalers. The overwhelming interest of researchers in the function of the Hippo pathway in stem cells and cancer prompted us to seek a larger forum. At the Keystone Symposia meeting on The Hippo Tumor Suppressor Network we aim to: (i) Define why YAP and TAZ function as either oncogenes or tumor suppressors; (ii) Identify membrane complexes, which activate the Hippo pathway in mammals, as the orthology with the fly receptors is not clear; (iii) Define targets for small molecule inhibitors and activators within pathway components based on structured modules, including WW, PDZ and SARAH domains. The meeting will be unique in bringing together Drosophila geneticists, basic and clinical cancer researchers, and the stem cell research community. We anticipate that this meeting will help to consolidate the emerging field and have an impact on development of new cancer therapies.

描述（由申请人提供）：请求对由Marius Sudol、Helen麦克尼尔、Georg A.哈尔德和乔瓦尼·布兰迪诺会议将于2013年5月19日至23日在加州蒙特雷举行。本次会议的主题与NCI的使命有关，即研究开发新的癌症疗法。此外，受邀在研讨会上发言的大多数是NCI支持的基础癌症研究人员。在过去的几年里，Hippo肿瘤抑制通路已经成为一个复杂的信号网络，对我们理解癌症发展和干细胞生物学的分子机制具有重要意义。该途径的主要效应物雅普和TAZ是转录共激活物，其充当干性因子和强效致癌基因。最近的研究表明，网络成分的异常表达可能导致癌症。因此，该途径及其网络分子是开发癌症药物和非常规治疗干预的有吸引力的靶标。近年来，该领域出现了几个悖论，该领域的快速进展在很大程度上是由于果蝇遗传学家和哺乳动物信号传导者之间的积极对话。研究人员对Hippo通路在干细胞和癌症中的功能的极大兴趣促使我们寻求更大的论坛。在关于Hippo肿瘤抑制剂网络的Keystone研讨会上，我们的目标是：（i）定义为什么雅普和TAZ作为癌基因或肿瘤抑制剂发挥作用;（ii）鉴定膜复合物，其激活哺乳动物中的Hippo通路，因为与苍蝇受体的同源性尚不清楚;（iii）基于结构化模块，包括WW、PDZ和SARAH结构域，在途径组分内定义小分子抑制剂和激活剂的靶标。这次会议将是独一无二的，汇集了果蝇遗传学家，基础和临床癌症研究人员，以及干细胞研究界。我们预计，本次会议将有助于巩固新兴领域，并对新的癌症疗法的发展产生影响。