Cell Differentiation within a Yeast Colony: Metabolic and Regulatory Parallels with a Tumor-Affected Organism
Cell Differentiation within a Yeast Colony: Metabolic and Regulatory Parallels with a Tumor-Affected Organism
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DOI：
10.1016/j.molcel.2012.04.001
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发表时间：
2012-05-25
期刊：
影响因子：
16
通讯作者：
Palkova, Zdena
中科院分区：
文献类型：
--
作者：
Cap, Michel;Stepanek, Ludek;Palkova, Zdena
营养感应和代谢重编程对后生动物细胞衰老和肿瘤生长至关重要。在这里，我们确定代谢和监管之间的平行分层，多细胞酵母菌群和肿瘤影响的有机体。在发育过程中，酵母菌菌落分层为U和L细胞，分别占据菌落的上部和下部区域。U细胞激活由谷氨酰胺诱导的TOR途径、氨基酸传感系统（SPS和Gcn 4p）和来自线粒体的信号传导控制的独特代谢，具有降低的呼吸。这些系统共同调节U细胞生理学，其适应营养限制并利用从L细胞释放的营养。抗应激U细胞与肿瘤细胞共享代谢途径和其他类似特征，包括增殖能力。L细胞的行为类似于应激和饥饿细胞，其激活降解机制以向U细胞提供营养。我们的数据表明两种细胞类型之间的营养流，类似于科里循环和谷氨酰胺-NH 4+穿梭于肿瘤和健康的多细胞动物细胞之间。
Nutrient sensing and metabolic reprogramming are crucial for metazoan cell aging and tumor growth. Here, we identify metabolic and regulatory parallels between a layered, multicellular yeast colony and a tumor-affected organism. During development, a yeast colony stratifies into U and L cells occupying the upper and lower colony regions, respectively. U cells activate a unique metabolism controlled by the glutamine-induced TOR pathway, amino acid-sensing systems (SPS and Gcn4p) and signaling from mitochondria with lowered respiration. These systems jointly modulate U cell physiology, which adapts to nutrient limitations and utilize the nutrients released from L cells. Stress-resistant U cells share metabolic pathways and other similar characteristics with tumor cells, including the ability to proliferate. L cells behave similarly to stressed and starving cells, which activate degradative mechanisms to provide nutrients to U cells. Our data suggest a nutrient flow between both cell types, resembling the Cori cycle and glutamine-NH4+ shuttle between tumor and healthy metazoan cells.