The role of entosis in human cancers

嵌入在人类癌症中的作用

基本信息

批准号：
9884740
负责人：
Michael H. Overholtzer
金额：
$ 42.17万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9884740
关键词：
Actomyosin Aneuploidy Autophagocytosis Breast Carcinoma Cell Adhesion Cell Adhesion Molecules Cell Death Cell Death Induction Cell Proliferation Cell Survival Cell-Cell Adhesion Cells Cellular Structures Colon Carcinoma Digestion Disease Progression Glucose Human Ingestion Link Lipids Lysosomes Malignant Neoplasms Malignant neoplasm of pancreas Mechanics Mediating Membrane Metabolic stress Molecular Nature Nutrient Orthologous Gene Pancreatic carcinoma Pathway interactions Population Process Protein Family Proteins Regulation Role Signal Transduction Starvation Stress Supporting Cell Tumorigenicity Vacuole Withdrawal Work adenylate kinase cancer cell cell killing deprivation experimental study malignant breast neoplasm novel nutrient deprivation programs public health relevance rho GTP-Binding Proteins tumor tumor progression tumorigenesis tumorigenic uptake

项目摘要

DESCRIPTION (provided by applicant): Recently a novel cell death mechanism occurring in cancer was described called entosis, where cancer cells were found to engulf and kill their neighbors through a non-apoptotic mechanism involving autophagy proteins and lysosome-mediated cell digestion. We have found that entosis has tumor-suppressive activity, linked to the induction of cell death, but also the ability to promote tumor progression, as this process induces aneuploidy, and provides cancer cells with nutrients that can support cell survival and proliferation. We have shown that this dual nature combines to make entosis a form of cell competition, where `winner' cells within a cancer cell population engulf and kill neighboring `loser' cells, and benefit from the nutrients that they scavenge. Here we propose to investigate our recent finding that metabolic stress, in the form of glucose withdrawal, is a strong inducer of entosis in cancer cell populations. This program therefore acts, similar to other homeostatic mechanisms such as autophagy, to allow cells to respond to starvation stress by recovering essential nutrients. Under conditions of glucose starvation, winner cells ingest losers and benefit from the nutrients that they recover, suggesting that glucose starvation induces a novel form of cell competition in cancers that is predicted to contribute significantly to disease progression. This proposal describes plans to elucidate the signaling mechanisms that control starvation-induced entosis and its effects on cancer progression.

描述（由申请人提供）：最近，癌症中发生的一种新的细胞死亡机制被称为“嵌入”，其中发现癌细胞通过涉及自噬蛋白和溶酶体介导的细胞消化的非凋亡机制吞噬并杀死其邻居。发现entosis具有肿瘤抑制活性，与诱导细胞死亡有关，而且还具有促进肿瘤进展的能力，因为这个过程会诱导非整倍性，并为癌细胞提供可以支持细胞生长的营养物质我们已经证明，这种双重性质结合起来使嵌入成为一种细胞竞争形式，癌细胞群中的“获胜者”细胞吞噬并杀死邻近的“失败者”细胞，并从它们清除的营养中受益。我们建议调查我们最近的发现，即以葡萄糖戒断形式出现的代谢应激是一种强烈的诱因因此，该程序与其他稳态机制（例如自噬）类似，可以让细胞通过恢复必需的营养物质来应对饥饿应激，在葡萄糖饥饿的情况下，胜利者细胞会吞噬失败者并从中受益。从它们恢复的营养中，葡萄糖饥饿会诱导癌症中一种新型的细胞竞争，预计这种竞争对疾病进展有显着贡献。该提案计划阐明控制饥饿诱导的内吞的信号机制及其对癌症的影响。进展。

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mitosis can drive cell cannibalism through entosis.

有丝分裂可以通过嵌入来驱动细胞同类相食。

DOI：
发表时间：
2017-07-11
期刊：
影响因子：
7.7
作者：
Durgan, Joanne;Tseng, Yun;Hamann, Jens C;Domart, Marie;Collinson, Lucy;Hall, Alan;Overholtzer, Michael;Florey, Oliver
通讯作者：
Florey, Oliver

Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes.

自噬机制通过靶向单膜介导巨内吞加工和内吞细胞死亡。