ArticleThe American journal of pathology2012
MAPK/ERK-dependent translation factor hyperactivation and dysregulated laminin γ2 expression in oral dysplasia and squamous cell carcinoma.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
- Expression of aquaporin 3 in squamous cell carcinoma in dogs and cats.The Journal of veterinary medical science · 2026Article
- Spatial transcriptomics reveals a molecular tumor budding signature in head and neck cancer.Genome medicine · 2026Article
- Laminin-gamma2 promotes oral squamous cell carcinoma growth by activating the p-ERK/c-Myc signaling pathway.BMC oral health · 2025Article
- Single-Cell and Spatial Transcriptomic Profiling of Penile Squamous Cell Carcinoma Reveals Dynamics of Tumor Differentiation and Immune Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The role of laminins in cancer pathobiology: a comprehensive review.Journal of translational medicine · 2025Review
- Cementum and enamel surface mimicry influences soft tissue cell behavior.Journal of periodontal research · 2025Article
- Upregulation of LY6K induced by FTO-mediated demethylation promotes the tumorigenesis and metastasis of oral squamous cell carcinoma via CAV-1-mediated ERK1/2 signaling activation.Histology and histopathology · 2024Article
- Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- VAV2 orchestrates the interplay between regenerative proliferation and ribogenesis in both keratinocytes and oral squamous cell carcinoma.Scientific reports · 2024Article
- Immortalization of patient-derived lip cells for establishing 3D lip models.Frontiers in cell and developmental biology · 2024Article
- Role of Microenvironmental Components in Head and Neck Squamous Cell Carcinoma.Journal of personalized medicine · 2023Review
- LAMC2 promotes EGFR cell membrane localization and acts as a novel biomarker for tyrosine kinase inhibitors (TKIs) sensitivity in lung cancer.Cancer gene therapy · 2023Article
- Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1.iScience · 2023Article
- Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights.Head and neck pathology · 2023Article
- Discovery and characterization of heterogeneous and multipotent fibroblast populations isolated from excised cleft lip tissue.Stem cell research & therapy · 2022Article
- The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview.International journal of molecular sciences · 2022Review
- Consistent downregulation of the cleft lip/palate-associated genesFrontiers in oncology · 2022Article
- Article
- Review
- A Living Cell Repository of the Cranio-/Orofacial Region to Advance Research and Promote Personalized Medicine.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Lesions displaying a variety of dysplastic changes precede invasive oral and epidermal squamous cell carcinoma (SCC); however, there are no histopathological criteria for either confirming or staging premalignancy. SCCs and dysplasias frequently contain cells that abnormally express the γ2 subunit of laminin-332. We developed cell culture models to investigate γ2 dysregulation. Normal human keratinocytes displayed density-dependent repression of γ2, whereas premalignant keratinocytes and SCC cells overexpressed γ2 and secreted laminin assembly intermediates. Neoplastic cells had hyperactive EGFR/MAPK(ERK) signaling coordinate with overexpressed γ2, and EGFR and MEK inhibitors normalized γ2 expression. Keratinocytes engineered to express HPV16 E6 or activated mutant HRAS, cRAF1, or MEK1 lost density repression of γ2 and shared with neoplastic cells signaling abnormalities downstream of ERK, including increased phosphorylation of S6 and eIF4 translation factors. Notably, qPCR results revealed that γ2 overexpression was not accompanied by increased γ2 mRNA levels, consistent with ERK-dependent, eIF4B-mediated translation initiation of the stem-looped, 5'-untranslated region of γ2 mRNA in neoplastic cells. Inhibitors of MEK, but not of TORC1/2, blocked S6 and eIF4B phosphorylation and γ2 overexpression. Immunostaining of oral dysplasias identified γ2 overexpression occurring within fields of basal cells that had elevated p-S6 levels. These results reveal a causal relationship between ERK-dependent translation factor activation and laminin γ2 dysregulation and identify new markers of preinvasive neoplastic change during progression to SCC.
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