ArticleMolecular cancer2021
Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
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- S-palmitoylation: a novel insight in the development and immunotherapy of oral squamous cell carcinoma.Journal of Cancer · 2025Review
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
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- Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing.Nature communications · 2024Article
- Transcription factor ATMIN facilitates chemoresistance in nasopharyngeal carcinoma.Cell death & disease · 2024Article
- Pathway of LCK Tyrosine Kinase and mTOR Signaling in Children with T-Cell Acute Lymphoblastic Leukemia.The application of clinical genetics · 2024Review
- Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.Frontiers in immunology · 2024Article
- Metabolic Patterns of High-Invasive and Low-Invasive Oral Squamous Cell Carcinoma Cells Using Quantitative Metabolomics andBiomolecules · 2023Article
- A novel prognostic NScientific reports · 2023Article
- Correction: Identification of lymphocyte cell-specific protein-tyrosine kinase (LCK) as a driver for invasion and migration of oral cancer by tumor heterogeneity exploitation.Molecular cancer · 2023Article
- Transcriptomic Analysis of Subtype-Specific Tyrosine Kinases as Triple Negative Breast Cancer Biomarkers.Cancers · 2023Article
- Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.International journal of molecular sciences · 2022Article
- Lucidenic acid A inhibits the binding of hACE2 receptor with spike protein to prevent SARS-CoV-2 invasion.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Article
- Definition and verification of novel metastasis and recurrence related signatures of ccRCC: A multicohort study.Cancer innovation · 2022Article
- Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma.Biomolecules · 2022Article
- Integrative network-based approaches identified systems-level molecular signatures associated with gallbladder cancer pathogenesis from gallstone diseases.Journal of biosciences · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer metastases are the main cause of lethality. The five-year survival rate for patients diagnosed with advanced stage oral cancer is 30%. Hence, the identification of novel therapeutic targets is an urgent need. However, tumors are comprised of a heterogeneous collection of cells with distinct genetic and molecular profiles that can differentially promote metastasis making therapy development a challenging task. Here, we leveraged intratumoral heterogeneity in order to identify drivers of cancer cell motility that might be druggable targets for anti-metastasis therapy.
methodsWe used 2D migration and 3D matrigel-based invasion assays to characterize the invasive heterogeneity among and within four human oral cancer cell lines in vitro. Subsequently, we applied mRNA-sequencing to map the transcriptomes of poorly and strongly invasive subclones as well as primary tumors and matched metastasis.
resultsWe identified SAS cells as a highly invasive oral cancer cell line. Clonal analysis of SAS yielded a panel of 20 subclones with different invasive capacities. Integrative gene expression analysis identified the Lymphocyte cell-specific protein-tyrosine kinase (LCK) as a druggable target gene associated with cancer cell invasion and metastasis. Inhibition of LCK using A-770041 or dasatinib blocked invasion of highly aggressive SAS cells. Interestingly, reduction of LCK activity increased the formation of adherens junctions and induced cell differentiation.
conclusionAnalysis of invasive heterogeneity led to the discovery of LCK as an important regulator of motility in oral cancer cells. Hence, small molecule mediated inhibition of LCK could be a promising anti-metastasis therapy option for oral cancer patients.
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