ArticleThe Journal of experimental medicine2021
Squamous cell carcinoma subverts adjacent histologically normal epithelium to promote lateral invasion.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Characterization of the immune response in patients with cancer of the oral cavity after neoadjuvant immunotherapy with the IRX-2 regimen.Oral oncology · 2021Trial
- Loss of salivary agglutinin induces changes in the salivary microbiome and accelerates development of oral cancer.Microbiome · 2026Article
- Splicing of HPV16 E6 promotes aggressive invasion in oropharyngeal cancer via endocytosis of E-cadherin.bioRxiv : the preprint server for biology · 2025Article
- Clinico-tomographic-pathological correlation in nodulo-ulcerative ocular surface squamous neoplasia: a study of 16 cases.International ophthalmology · 2025Article
- Article
- Salivary microbiome changes distinguish response to chemoradiotherapy in patients with oral cancer.Microbiome · 2023Article
- Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma.Nature communications · 2023Article
- Heparan-6-Cancers · 2023Article
- Cytokines secreted by inflamed oral mucosa: implications for oral cancer progression.Oncogene · 2023Review
- The mouse oral carcinoma (MOC) model: A 10-year retrospective on model development and head and neck cancer investigations.Oral oncology · 2022Review
- Epithelial-Mesenchymal Plasticity in Tumor Immune Evasion.Cancer research · 2022Review
- Epidermal growth factor receptor signaling in precancerous keratinocytes promotes neighboring head and neck cancer squamous cell carcinoma cancer stem cell-like properties and phosphoinositide 3-kinase inhibitor insensitivity.Molecular carcinogenesis · 2022Article
- Review
- Cancer-associated keratinocytes: new members of the microenvironment in head and neck cancer.Molecular & cellular oncology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Recurrent and new tumors, attributed in part to lateral invasion, are frequent in squamous cell carcinomas and lead to poor survival. We identified a mechanism by which cancer subverts adjacent histologically normal epithelium to enable small clusters of cancer cells to burrow undetected under adjacent histologically normal epithelium. We show that suppression of DMBT1 within cancer promotes aggressive invasion and metastasis in vivo and is associated with metastasis in patients. Cancer cells via TGFβ1 and TNFα also suppress DMBT1 in adjacent histologically normal epithelium, thereby subverting it to promote invasion of a small population of tumor cells. The sufficiency of DMBT1 in this process is demonstrated by significantly higher satellite tumor nests in Dmbt1-/- compared with wild-type mice. Moreover, in patients, invasion of small tumor nests under adjacent histologically normal epithelium is associated with increased risk for recurrence and shorter disease-free survival. This study demonstrates a crucial role of adjacent histologically normal epithelium in invasion and its important role in the tumor microenvironment and opens new possibilities for therapeutic strategies that reduce tumor recurrence.
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Registered trials
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