ArticleJournal of experimental & clinical cancer research : CR2019
A novel miR-365-3p/EHF/keratin 16 axis promotes oral squamous cell carcinoma metastasis, cancer stemness and drug resistance via enhancing β5-integrin/c-met signaling 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 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Diagnostic and Prognostic Value of MicroRNAs in Metastasis and Recurrence of Head and Neck Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Article
- CircNOLC1/KRT16 promotes colorectal cancer invasion and migration via c-met nuclear translocation and reprogramming of the oxidative pentose phosphate pathway.The Journal of biological chemistry · 2026Article
- Reference-free discovery with barcoded single-cell sequencing.Nature biotechnology · 2026Article
- KRT81 promotes metastasis of colorectal cancer by acting as a protein scaffold for ezrin.Oncogene · 2026Article
- Integrin β3: structural functions, tumour microenvironment regulatory roles and targeted intervention strategies.Frontiers in immunology · 2026Review
- DNA methylation-wide association study of prevalent and incident dementia in the US Health and Retirement Study.medRxiv : the preprint server for health sciences · 2025Article
- Diagnostic and therapeutic potential of oral cavity-derived exosomes in oral and maxillofacial tissue engineering: current advances and future perspectives.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Oral squamous cell carcinoma: Insights into cellular heterogeneity, drug resistance, and evolutionary trajectories.Cell biology and toxicology · 2025Review
- A novel efferocytosis-related gene signature for predicting prognosis and therapeutic response in bladder cancer.Scientific reports · 2025Article
- Role of M2 macrophage-derived exosomes in cancer drug resistance via noncoding RNAs.Discover oncology · 2025Review
- MiR-365-3p inhibits lung cancer proliferation and migration via CPT1A-mediated fatty acid oxidation.Scientific reports · 2025Article
- Article
- Metabolic biomarker in oral squamous cell carcinoma - a comprehensive review.GMS Interdisciplinary plastic and reconstructive surgery DGPW · 2025Review
- The MET Oncogene Network of Interacting Cell Surface Proteins.International journal of molecular sciences · 2024Review
- miR-195-5p Inhibits Colon Cancer Progression via KRT23 Regulation.Pharmaceutics · 2024Article
- Review
- Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis.Cellular & molecular biology letters · 2024Article
- Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.Cancer cell international · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundTargeting the c-Met signaling pathway has become a therapeutic strategy in multiple types of cancer. We unveiled a novel c-Met regulating mechanism that could be applied as a modality for oral squamous cell carcinoma (OSCC) therapy.
methodsUpregulation of keratin 16 (KRT16) was found by comparing isogenic pairs of low and high invasive human OSCC lines via microarray analysis. OSCC cells with ectopic expression or silencing of KRT16 were used to scrutinize functional roles and associated molecular mechanisms.
resultsWe observed that high KRT16 expression significantly correlated with poorer pathological differentiation, advanced stages, increased lymph nodes metastasis, and decreased survival rate from several Taiwanese OSCC patient cohorts. We further revealed that miR-365-3p could target ETS homologous factor (EHF), a KRT16 transcription factor, to decrease migration, invasion, metastasis and chemoresistance in OSCC cells via inhibition of KRT16. Under confocal microscopic examination, c-Met was found possibly partially associates with KRT16 through β5-integrin. Colocalization of these three proteins may facilitate c-Met and β5-integrin-mediated signaling in OSCC cells. Depletion of KRT16 led to increased protein degradation of β5-integrin and c-Met through a lysosomal pathway leading to inhibition of their downstream Src/STAT3/FAK/ERK signaling in OSCC cells. Knockdown of KRT16 enhanced chemosensitivity of OSCC towards 5-fluorouracil (5-FU). Various combination of c-Met inhibitor (foretinib), protein tyrosine kinase inhibitor (genistein), β5-integrin antibody, and 5-FU markedly augmented cytotoxic effects in OSCC cells as well as tumor killing effects in vitro and in vivo.
conclusionsOur data indicate that targeting a novel miR-365-3p/EHF/KRT16/β5-integrin/c-Met signaling pathway could improve treatment efficacy in OSCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.