The role of entosis in human cancers

嵌入在人类癌症中的作用

• 批准号: 9249491
• 负责人: Michael H. Overholtzer
• 金额: $ 39.73万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 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/9249491
• 关键词: Actomyosin; Alpha Cell; Aneuploidy; Autophagocytosis; Breast Carcinoma; Cell Adhesion; Cell Death; Cell Death Induction; Cell Proliferation; Cell Survival; Cell-Cell Adhesion; Cells; Cellular Structures; Colon Carcinoma; Digestion; Disease Progression; Glucose; Human; 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; killings; malignant breast neoplasm; novel; nutrient deprivation; programs; public health relevance; rho GTP-Binding Proteins; tumor; tumor progression; tumorigenesis; tumorigenic; uptake

 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.