Related Experiment Video
Updated: Jun 2, 2026
Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay
Published on: August 14, 2018
Identification of an exon 4-deletion variant of epidermal growth factor receptor with increased metastasis-promoting
Hai Wang1, Min Zhou, Bizhi Shi
1State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Cancer Institute.
Abstract:
Several types of epidermal growth factor receptor (EGFR) gene alternations have been observed in human tumors. Here we present a novel EGFR variant with aberrant splicing of exon 4 (named as de4 EGFR). Variant-specific polymerase chain reaction showed that de4 EGFR was expressed in some glioma (4/40), prostate cancer (3/11), and ovarian cancer (3/9) tissues but not in tissues adjacent to tumors or normal tissues. de4 EGFR displayed an enhanced transformation and a higher metastasis-promoting capacity in comparison to wild-type EGFR. With minimal EGF-binding activity, de4 EGFR underwent ligand-independent autophosphorylation and self-dimerization. Moreover, in serum-starved condition, de4 EGFR expression in U87 MG cells significantly upregulated the extracellular signal-regulated kinase and AKT phosphorylation and expression of JUN and Src. Importantly, E-cadherin expression was barely detectable in the U87 MG cells expressing de4 EGFR and restored expression of E-cadherin in these cells inhibited their metastatic behaviors. Taken together, we identified a novel EGFR variant with increased metastasis-promoting activity that may become a promising new target for cancer therapy.
Insights
A novel epidermal growth factor receptor (EGFR) variant, de4 EGFR, promotes cancer metastasis. This de4 EGFR variant, found in glioma, prostate, and ovarian cancers, offers a potential new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Epidermal growth factor receptor (EGFR) gene alterations are common in human tumors.
- Aberrant splicing of EGFR can lead to novel variants with altered functions.
Purpose of the Study:
- To identify and characterize a novel EGFR variant with aberrant splicing.
- To investigate the functional role of this variant in cancer progression and metastasis.
Main Methods:
- Variant-specific polymerase chain reaction (PCR) to detect de4 EGFR.
- In vitro assays to assess transformation and metastasis-promoting capacity.
- Western blotting to analyze protein phosphorylation and expression.
Main Results:
- A novel de4 EGFR variant was identified in glioma, prostate, and ovarian cancer tissues.
- de4 EGFR exhibited enhanced transformation and metastasis-promoting activity compared to wild-type EGFR.
- de4 EGFR promoted ligand-independent activation of signaling pathways (ERK, AKT, JUN, Src) and reduced E-cadherin expression, facilitating metastasis.
Conclusions:
- The de4 EGFR variant is a novel oncogenic driver with significant metastasis-promoting activity.
- de4 EGFR may represent a promising therapeutic target for cancers exhibiting its expression.
Related Concept Videos
02:38Mitogens and the Cell Cycle
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...