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Revealing new molecular pathways for cancer cell fitness through a genetic screen of the cancer translatome

ABSTRACT: Revealing new molecular pathways for cancer cell fitness through a genetic screen of the cancer translatome

PROVIDER: PRJNA732363 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14631668_1.fastq.gz	Fastqsanger.gz
	SRR14631668_2.fastq.gz	Fastqsanger.gz
	SRR14631669_1.fastq.gz	Fastqsanger.gz
	SRR14631669_2.fastq.gz	Fastqsanger.gz
	SRR14631670_1.fastq.gz	Fastqsanger.gz

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Revealing new molecular pathways for cancer cell fitness through a genetic screen of the cancer translatome

Project description:The major cap binding protein eIF4E, an ancient protein required for translation of all eukaryotic genomes, is a surprising yet potent oncogenic driver. The genetic interactions that maintain the oncogenic activity of this key translation factor remain unknown. Here we carried out a genome-wide CRISPRi screen wherein we identified over 600 genetic interactions that sustain eIF4E oncogenic activity. Our data show that eIF4E controls the translation of Tfeb, a key executer of the autophagy response. This autophagy survival response is triggered by mitochondrial proteotoxic stress, which allows cancer cell survival. Our screen also reveals a functional interaction between eIF4E and a single anti-apoptotic factor, Bcl-xL, in tumor growth. Furthermore, we show that eIF4E and the exon-junction complex (EJC), involved in many steps of RNA metabolism, interact to control the migratory properties of cancer cells. Overall, we have uncovered several cancer-specific vulnerabilities that provide unprecedented resolution of the cancer translatome.

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