The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression

Cho Rong Park, Dong Joo You, Sumi Park, Sunam Mander, Da Eun Jang, Su Cheong Yeom, Seong Hyun Oh, Curie Ahn, Sang Heon Lee, Jae Young Seong, Jong-Ik Hwang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses. In A549 lung cancer cells, which endogenously express CXCR1, the depletion of REEP5 and REEP6 significantly reduced growth and invasion by downregulating IL-8-stimulated ERK phosphorylation, actin polymerization and the expression of genes related to metastasis. Furthermore, an in vivo xenograft model showed that proliferation and metastasis of A549 cells lacking REEP5 and REEP6 were markedly decreased compared to the control group. Thus, REEP5 and REEP6 could be novel regulators of G-protein-coupled receptor signaling whose functional mechanisms differ from other accessory proteins.

Original languageEnglish
Article number39041
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Dec 14

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Interleukin-8
Lung Neoplasms
G-Protein-Coupled Receptors
Down-Regulation
Neoplasm Metastasis
Proteins
Endocytosis
Heterografts
Polymerization
Cluster Analysis
Actins
Phosphorylation
Cell Membrane
Ligands
Gene Expression
Control Groups
Membranes
Growth

ASJC Scopus subject areas

  • General

Cite this

The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression. / Park, Cho Rong; You, Dong Joo; Park, Sumi; Mander, Sunam; Jang, Da Eun; Yeom, Su Cheong; Oh, Seong Hyun; Ahn, Curie; Lee, Sang Heon; Seong, Jae Young; Hwang, Jong-Ik.

In: Scientific Reports, Vol. 6, 39041, 14.12.2016.

Research output: Contribution to journalArticle

Park, Cho Rong ; You, Dong Joo ; Park, Sumi ; Mander, Sunam ; Jang, Da Eun ; Yeom, Su Cheong ; Oh, Seong Hyun ; Ahn, Curie ; Lee, Sang Heon ; Seong, Jae Young ; Hwang, Jong-Ik. / The accessory proteins REEP5 and REEP6 refine CXCR1-mediated cellular responses and lung cancer progression. In: Scientific Reports. 2016 ; Vol. 6.
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AU - Yeom, Su Cheong

AU - Oh, Seong Hyun

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