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Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes

ABSTRACT: The involvement of G-Protein-Coupled Receptors’ (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, capable of signaling intranuclearly to induce nuclear-ERK and AKT phosphorylation concomitant with higher cancer cell proliferation and survival. We determine its nuclear interactome, proving its involvement in protein-translation and DNA-damage repair. Nuclear HCAR1 (N-HCAR1) directly interacts with chromatin/DNA promoting expression of genes involved in cellular migration. Notably, we show N-HCAR1 particularly regulates a broader transcriptomic signature than its plasma membrane counterpart, emphasizing on the facts that functional output of N-HCAR1 is larger than plasma membrane localized HCAR1. Our study presents several unprecedented processes by which a GPCR through location-biased activity regulate various cellular functions and how cancer cells exploit these.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Eric Bonneil

LAB HEAD: Sylvain Chemtob

PROVIDER: PXD035882 | Pride | 2025-01-22

REPOSITORIES: pride

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			Action	DRS
	Service_Chemtob_170619_1.mgf	Mgf
	Service_Chemtob_170619_1.raw	Raw
	Service_Chemtob_170619_2.mgf	Mgf
	Service_Chemtob_170619_2.mzid.gz	Mzid
	Service_Chemtob_170619_2.raw	Raw

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Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes

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