GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma

Metastasis is a leading cause of lung adenocarcinoma (LUAD)-related mortality and presents significant challenges for treatment. The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor (GPCR) family, has an unclear role in LUAD progression. This study aimed to inves...

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Main Authors: Dong-Gun Kim, Eun-Young Choi, Hye-Mi Ahn, Youn-Jae Kim
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/24/2128
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author Dong-Gun Kim
Eun-Young Choi
Hye-Mi Ahn
Youn-Jae Kim
author_facet Dong-Gun Kim
Eun-Young Choi
Hye-Mi Ahn
Youn-Jae Kim
author_sort Dong-Gun Kim
collection DOAJ
description Metastasis is a leading cause of lung adenocarcinoma (LUAD)-related mortality and presents significant challenges for treatment. The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor (GPCR) family, has an unclear role in LUAD progression. This study aimed to investigate the function and underlying mechanisms of GRPR in LUAD metastasis. Our findings revealed that GRPR levels were significantly elevated in tumor tissues, and higher <i>GRPR</i> expression was associated with worse overall survival outcomes. Functional assays demonstrated that <i>GRPR</i> overexpression enhanced LUAD cell invasion, while <i>GRPR</i> knockdown inhibited invasion both in vitro and in vivo. RNA sequencing and gene set enrichment analysis (GSEA) identified an enrichment of metastasis-promoting genes in <i>GRPR</i>-overexpressing cells, with CRABP2 and FNDC4 emerging as key targets. Clinical analyses further confirmed a positive correlation between <i>GRPR</i> expression and the levels of <i>CRABP2</i> and <i>FNDC4</i> in LUAD patients. These results suggest that GRPR could serve as both a prognostic marker and a therapeutic target to inhibit metastasis in LUAD.
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spelling doaj-art-c3b64259d44845edb877b935861ab2e42025-08-20T02:00:43ZengMDPI AGCells2073-44092024-12-011324212810.3390/cells13242128GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung AdenocarcinomaDong-Gun Kim0Eun-Young Choi1Hye-Mi Ahn2Youn-Jae Kim3Targeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaTargeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaTargeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaTargeted Therapy Branch, Division of Rare and Refractory Cancer, Research Institute, National Cancer Center, Goyang 10408, Republic of KoreaMetastasis is a leading cause of lung adenocarcinoma (LUAD)-related mortality and presents significant challenges for treatment. The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor (GPCR) family, has an unclear role in LUAD progression. This study aimed to investigate the function and underlying mechanisms of GRPR in LUAD metastasis. Our findings revealed that GRPR levels were significantly elevated in tumor tissues, and higher <i>GRPR</i> expression was associated with worse overall survival outcomes. Functional assays demonstrated that <i>GRPR</i> overexpression enhanced LUAD cell invasion, while <i>GRPR</i> knockdown inhibited invasion both in vitro and in vivo. RNA sequencing and gene set enrichment analysis (GSEA) identified an enrichment of metastasis-promoting genes in <i>GRPR</i>-overexpressing cells, with CRABP2 and FNDC4 emerging as key targets. Clinical analyses further confirmed a positive correlation between <i>GRPR</i> expression and the levels of <i>CRABP2</i> and <i>FNDC4</i> in LUAD patients. These results suggest that GRPR could serve as both a prognostic marker and a therapeutic target to inhibit metastasis in LUAD.https://www.mdpi.com/2073-4409/13/24/2128lung adenocarcinomametastasisGRPRAKTCRAPB2FNCD4
spellingShingle Dong-Gun Kim
Eun-Young Choi
Hye-Mi Ahn
Youn-Jae Kim
GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
Cells
lung adenocarcinoma
metastasis
GRPR
AKT
CRAPB2
FNCD4
title GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
title_full GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
title_fullStr GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
title_full_unstemmed GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
title_short GRPR Drives Metastasis via CRABP2 and FNDC4 Pathways in Lung Adenocarcinoma
title_sort grpr drives metastasis via crabp2 and fndc4 pathways in lung adenocarcinoma
topic lung adenocarcinoma
metastasis
GRPR
AKT
CRAPB2
FNCD4
url https://www.mdpi.com/2073-4409/13/24/2128
work_keys_str_mv AT donggunkim grprdrivesmetastasisviacrabp2andfndc4pathwaysinlungadenocarcinoma
AT eunyoungchoi grprdrivesmetastasisviacrabp2andfndc4pathwaysinlungadenocarcinoma
AT hyemiahn grprdrivesmetastasisviacrabp2andfndc4pathwaysinlungadenocarcinoma
AT younjaekim grprdrivesmetastasisviacrabp2andfndc4pathwaysinlungadenocarcinoma