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PSMG2-controlled proteasome-autophagy balance mediates the tolerance for MEK targeted therapy in TNBC

ABSTRACT: PSMG2-controlled proteasome-autophagy balance mediates the tolerance for MEK targeted therapy in TNBC

PROVIDER: PRJNA851966 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19792342_1.fastq.gz	Fastqsanger.gz
	SRR19792342_2.fastq.gz	Fastqsanger.gz
	SRR19792343_1.fastq.gz	Fastqsanger.gz
	SRR19792343_2.fastq.gz	Fastqsanger.gz
	SRR19792344_1.fastq.gz	Fastqsanger.gz

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PSMG2-controlled proteasome-autophagy balance mediates the tolerance for MEK targeted therapy in TNBC

Project description:We performed an unbiased genome-wide CRISPR/Cas9 knockout screening to identify synergistic drug targets in TNBC cells with MEK inhibitor. PSMG2 was found as a critical synthetically lethal gene with MEK inhibition. Mechanism investigation unraveled that PSMG2 knockdown inhibited proteasome function, which in turn activated cell autophagy. Autophagy, unlike its function in chemoresistance, inhibited PI3K/AKT pathway by specific degradation of PDPK1. Co-targeting MAPK pathway and proteasome pathway synergistically suppressed TNBC cells proliferation in vitro and in vivo.

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Proteasome gene expression is controlled by the coordinated functions of multiple transcription factors

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