生物
细胞生物学
线粒体
线粒体分裂
癌症研究
转移
癌症
遗传学
作者
Ekta Agarwal,Brian J. Altman,Jae Ho Seo,Irene Bertolini,Jagadish C. Ghosh,Amanpreet Kaur,Andrew V. Kossenkov,Lucia R. Languino,Dmitry I. Gabrilovich,David W. Speicher,Chi V. Dang,Dario C. Altieri
摘要
The Myc gene is a universal oncogene that promotes aggressive cancer, but its role in metastasis has remained elusive. Here, we show that Myc transcriptionally controls a gene network of subcellular mitochondrial trafficking that includes the atypical mitochondrial GTPases RHOT1 and RHOT2, the adapter protein TRAK2, the anterograde motor Kif5B, and an effector of mitochondrial fission, Drp1. Interference with this pathway deregulates mitochondrial dynamics, shuts off subcellular organelle movements, and prevents the recruitment of mitochondria to the cortical cytoskeleton of tumor cells. In turn, this inhibits tumor chemotaxis, blocks cell invasion, and prevents metastatic spreading in preclinical models. Therefore, Myc regulation of mitochondrial trafficking enables tumor cell motility and metastasis.
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