细胞外基质
肿瘤微环境
癌细胞
串扰
谷氨酰胺
生物
肿瘤进展
细胞代谢
癌症
细胞生物学
细胞生长
癌症研究
基质
糖酵解
代谢途径
谷氨酰胺分解
新陈代谢
生物化学
肿瘤细胞
氨基酸
免疫学
遗传学
物理
免疫组织化学
光学
作者
Thomas Bertero,William M. Oldham,Eloïse M. Grasset,Isabelle Bourget,Etienne Boulter,Sabrina Pisano,Paul Hofman,Floriant Bellvert,Guerrino Meneguzzi,Dmitry V. Bulavin,Soline Estrach,Chloé C. Féral,Stephen Y. Chan,Alexandre Bozec,Cédric Gaggioli
出处
期刊:Cell Metabolism
[Elsevier]
日期:2019-01-01
卷期号:29 (1): 124-140.e10
被引量:265
标识
DOI:10.1016/j.cmet.2018.09.012
摘要
Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino acid flux within the tumor niche. Specifically, we demonstrate a metabolic crosstalk between CAF and cancer cells in which CAF-derived aspartate sustains cancer cell proliferation, while cancer cell-derived glutamate balances the redox state of CAFs to promote ECM remodeling. Collectively, our findings link mechanical stimuli to dysregulated tumor metabolism and thereby highlight a new metabolic network within tumors in which diverse fuel sources are used to promote growth and aggressiveness. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in cancer.
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