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KCNQ POTASSIUM CHANNELS MODULATE WNT ACTIVITY IN GASTRO-OESOPHAGEAL ADENOCARCINOMAS

ABSTRACT: KCNQ POTASSIUM CHANNELS MODULATE WNT ACTIVITY IN GASTRO-OESOPHAGEAL ADENOCARCINOMAS

PROVIDER: PRJNA1014713 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25993031.fastq.gz	Fastqsanger.gz
	SRR25993032.fastq.gz	Fastqsanger.gz
	SRR25993033.fastq.gz	Fastqsanger.gz
	SRR25993034.fastq.gz	Fastqsanger.gz
	SRR25993035.fastq.gz	Fastqsanger.gz

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KCNQ POTASSIUM CHANNELS MODULATE WNT ACTIVITY IN GASTRO-OESOPHAGEAL ADENOCARCINOMAS

Project description:Voltage sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large scale analysis of 897 patients with Gastro-oesophageal adenocarcincomas (GOA) coupled with in vitro models, we find KCNQ family genes are mutated in ~30% of patients, and play therapeutically targetable roles in GOA cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation through resultant effects on cadherins junctions. This also highlights novel roles for KCNQ3 in non-excitable tissues. We additionally discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors, and that inhibition of KCNQ activity reduces proliferation of GOA cancer cells. These findings reveal a novel and exploitable role for potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GOAs may exist through KCNQ inhibitors.

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Mechanism of pharmacochaperoning in ATP-sensitive potassium channels revealed by cryo-EM

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