ArticleJournal of experimental & clinical cancer research : CR2019
GPAA1 promotes gastric cancer progression via upregulation of GPI-anchored protein and enhancement of ERBB signalling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Integrative analysis identifies PIGK as an oncogenic glycosylphosphatidylinositol transamidase subunit with prognostic, immunological, and therapeutic relevance in head and neck cancer.International journal of medical sciences · 2026Article
- Metabolic traits shape responses to LSD1-directed therapy in glioblastoma tumor-initiating cells.Science advances · 2025Article
- The ubiquitin ligase RCBTB2 regulates aggrephagy and inhibits prostate cancer progression by targeting GPAA1 for degradation.American journal of cancer research · 2025Article
- Mechanistic insights into GPAA1-mediated cold tumor phenotype and immune evasion in colorectal cancer: integrative multi-omics analysis and experimental validation.Frontiers in oncology · 2025Article
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- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Structure and Function of the Glycosylphosphatidylinositol Transamidase, a Transmembrane Complex Catalyzing GPI Anchoring of Proteins.Sub-cellular biochemistry · 2024Review
- Glycosylphosphatidylinositol anchor biosynthesis pathway-based biomarker identification with machine learning for prognosis and T cell exhaustion status prediction in breast cancer.Frontiers in immunology · 2024Article
- [Glycosylphosphatidylinositol biosynthesis deficiency 15 caused byZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2023Article
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- FMR1 promotes the progression of colorectal cancer cell by stabilizing EGFR mRNA in an mCell death & disease · 2022Article
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- GPAA1 promotes the proliferation, invasion and migration of hepatocellular carcinoma cells by binding to RNA-binding protein SF3B4.Oncology letters · 2022Article
- Prognostic Signature and Therapeutic Value Based on Membrane Lipid Biosynthesis-Related Genes in Breast Cancer.Journal of oncology · 2022Article
- Integrated multi-omics analysis identifiesFrontiers in oncology · 2022Article
- Proteomic-Based Machine Learning Analysis Reveals PYGB as a Novel Immunohistochemical Biomarker to Distinguish Inverted Urothelial Papilloma From Low-Grade Papillary Urothelial Carcinoma With Inverted Growth.Frontiers in oncology · 2022Article
- Data-independent acquisition-based proteome and phosphoproteome profiling across six melanoma cell lines reveals determinants of proteotypes.Molecular omics · 2021Article
- Comprehensive Analysis of the Glycolysis-Related Gene Prognostic Signature and Immune Infiltration in Endometrial Cancer.Frontiers in cell and developmental biology · 2021Article
- Article
- Identification and Validation of Prognostically Relevant Gene Signature in Melanoma.BioMed research international · 2020Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundGastric cancer is one of the deadliest malignant tumours, with a high incidence in China, and is regulated by aberrantly overexpressed oncogenes. However, existing therapies are insufficient to meet patients' needs; thus, the identification of additional therapeutic targets and exploration of the underlying mechanism are urgently needed. GPAA1 is the subunit of the GPI transamidase that transfers the GPI anchor to proteins within the ER. The functional impacts of increased expression levels of GPAA1 in human cancers are not well understood.
methodsData mining was performed to determine the pattern of GPAA1 expression and the reason for its overexpression in tumour and adjacent normal tissues. In vitro and in vivo experiments evaluating proliferation and metastasis were performed using cells with stable deletion or overexpression of GPAA1. A tissue microarray established by the Ren Ji Hospital was utilized to analyse the expression profile of GPAA1 and its correlation with prognosis. Western blotting, an in situ proximity ligation assay, and co-immunoprecipitation (co-IP) were performed to reveal the mechanism of GPAA1 in gastric cancer.
resultsGPAA1 was a markedly upregulated oncogene in gastric cancer due to chromosomal amplification. GPAA1 overexpression was confirmed in specimens from the Ren Ji cohort and was associated with ERBB2 expression, predicting unsatisfactory patient outcomes. Aberrantly upregulated GPAA1 dramatically contributed to cancer growth and metastasis in in vitro and in vivo studies. Mechanistically, GPAA1 enhanced the levels of metastasis-associated GPI-anchored proteins to increase tumour metastasis and intensified lipid raft formation, which consequently promoted the interaction between EGFR and ERBB2 as well as downstream pro-proliferative signalling.
conclusionsGPAA1 facilitates the expression of cancer-related GPI-anchored proteins and supplies a more robust platform-the lipid raft-to promote EGFR-ERBB2 dimerization, which further contributes to tumour growth and metastasis and to cancer progression. GPAA1 could be a promising diagnostic biomarker and therapeutic target for gastric cancer.
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