Regulated cell death and responses to starvation in cancer

癌症中细胞死亡的调节和饥饿反应

• 批准号: 10701815
• 负责人: Michael H. Overholtzer
• 金额: $ 90.18万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2029-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10701815
• 关键词: Area; Biological; Cell Death; Cell Survival; Cells; Cellular Stress; Equilibrium; Image; Knowledge; Lysosomes; Malignant Neoplasms; Methods; Normal Cell; Nutrient; Population; Population Control; Population Dynamics; Research; Starvation; Stress; biological adaptation to stress; cancer cell; cancer therapy; programs; response; targeted cancer therapy; treatment response; tumor microenvironment

Abstract Cells respond to stress by upregulating adaptive mechanisms that promote survival or by undergoing cell death when the stress is too severe. Cancer cells take advantage of stress responses in order to survive within harsh cancer microenvironments, and understanding which adaptive mechanisms are utilized to avoid cell death is critical to gaining new knowledge that may be exploited for cancer therapy. It has also become clear that there is not one, but in fact many different forms of cell death that can occur in response to stress, and our studies have contributed significantly in this area. We have shown that some mechanisms have unique effects on the dynamics of cell populations, and that some promote, while others may hinder, therapeutic responses. Our proposed research program will focus on two major areas of discovery: (1) How is cell death regulated in response to stress, and how do particular mechanisms contribute to controlling population dynamics? (2) How do cells respond to nutrient starvation through adaptive mechanisms that involve lysosomes? We will exploit recent findings and methods we have developed to study these overarching questions through an integrated set of cell biological approaches with a focus on imaging-based studies.

抽象的 细胞通过上调促进生存或通过的适应机制来应对压力 当压力太严重时，会经历细胞死亡。癌细胞利用压力 回答以在恶劣的癌症微环境中生存，并了解哪个 自适应机制用于避免细胞死亡对于获得可能的新知识至关重要 被利用用于癌症治疗。也很明显，没有一个，但实际上很多 可以响应压力而发生的不同形式的细胞死亡，我们的研究也有助于 在这一领域很重要。我们已经表明，某些机制对 细胞群体的动态，有些促进，而另一些人可能会阻碍治疗 回答。我们提出的研究计划将重点关注发现的两个主要领域：（1） 细胞死亡是否应响应压力，以及特定机制如何促成 控制人口动态？ （2）细胞如何通过自适应对营养饥饿做出反应 涉及溶酶体的机制？我们将利用我们拥有的最新发现和方法 开发用于通过一组整体的细胞生物学研究这些总体问题 侧重于基于成像的研究的方法。