ArticleMolecular cancer2014
EGFR phosphorylates and inhibits lung tumor suppressor GPRC5A in lung cancer.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- G protein-coupled receptors as novel therapeutic targets in non-small-cell lung cancer.Medical review (2021) · 2025Review
- Vitamin D and Retinoic Acid Require Protein Kinase C Activity and Reactive Oxygen Species as Opposing Signals RegulatingBiomolecules · 2025Article
- Article
- Exploring the Prognostic Value and Immune Infiltration Patterns of GPRC5A Across Multiple Cancer Types.Journal of Cancer · 2024Article
- RAI3 expression is not associated with clinical outcomes of patients with non-small cell lung cancer.Journal of cancer research and clinical oncology · 2023Article
- mViruses · 2023Article
- GPCR-mediated EGFR transactivation ameliorates skin toxicities induced by afatinib.Acta pharmacologica Sinica · 2022Article
- Signatures of malignant cells and novel therapeutic targets revealed by single-cell sequencing in lung adenocarcinoma.Cancer medicine · 2022Article
- Endogenous and Exogenous Regulatory Signaling in the Secretory Pathway: Role of Golgi Signaling Molecules in Cancer.Frontiers in cell and developmental biology · 2022Review
- Adaptive RSK-EphA2-GPRC5A signaling switch triggers chemotherapy resistance in ovarian cancer.EMBO molecular medicine · 2020Article
- Observational
- ALDH2 Repression Promotes Lung Tumor Progression via Accumulated Acetaldehyde and DNA Damage.Neoplasia (New York, N.Y.) · 2019Article
- GPRC5A: An Emerging Biomarker in Human Cancer.BioMed research international · 2018Review
- Quantitative phosphoproteomic analysis reveals reciprocal activation of receptor tyrosine kinases between cancer epithelial cells and stromal fibroblasts.Clinical proteomics · 2018Article
- Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion.Cell adhesion & migration · 2017Article
- Article
- Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research.International journal of molecular sciences · 2016Review
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Abstract
backgroundGPRC5A is a retinoic acid inducible gene that is preferentially expressed in lung tissue. Gprc5a- knockout mice develop spontaneous lung cancer, indicating Gprc5a is a lung tumor suppressor gene. GPRC5A expression is frequently suppressed in majority of non-small cell lung cancers (NSCLCs), however, elevated GPRC5A is still observed in a small portion of NSCLC cell lines and tumors, suggesting that the tumor suppressive function of GPRC5A is inhibited in these tumors by an unknown mechanism.
methodsIn this study, we examined EGF receptor (EGFR)-mediated interaction and tyrosine phosphorylation of GPRC5A by immunoprecipitation (IP)-Westernblot. Tyrosine phosphorylation of GPRC5A by EGFR was systematically identified by site-directed mutagenesis. Cell proliferation, migration, and anchorage-independent growth of NSCLC cell lines stably transfected with wild-type GPRC5A and mutants defective in tyrosine phosphorylation were assayed. Immunohistochemical (IHC) staining analysis with specific antibodies was performed to measure the total and phosphorylated GPRC5A in both normal lung and lung tumor tissues.
resultWe found that EGFR interacted with GPRC5A and phosphorylated it in two conserved double-tyrosine motifs, Y317/Y320 and Y347/ Y350, at the C-terminal tail of GPRC5A. EGF induced phosphorylation of GPRC5A, which disrupted GPRC5A-mediated suppression on anchorage-independent growth of NSCLC cells. On contrary, GPRC5A-4 F, in which the four tyrosine residues have been replaced with phenylalanine, was resistant to EGF-induced phosphorylation and maintained tumor suppressive activities. Importantly, IHC analysis with anti-Y317/Y320-P sites showed that GPRC5A was non-phosphorylated in normal lung tissue whereas it was highly tyrosine-phosphorylated in NSCLC tissues.
conclusionGPRC5A can be inactivated by receptor tyrosine kinase via tyrosine phosphorylation. Thus, targeting EGFR can restore the tumor suppressive functions of GPRC5A in lung cancer.
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