ArticleJournal of experimental & clinical cancer research : CR2022
LAMC2 marks a tumor-initiating cell population with an aggressive signature in pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Integrated multi-omics analysis reveals the molecular landscape and therapeutic strategies in Chinese cervical cancer patients.PLoS biology · 2026Article
- LAMC2Cancer science · 2026Article
- Isolation and Characterization of Extracellular Vesicles from Human and Mouse Pancreatic Tissue.Bioengineering (Basel, Switzerland) · 2026Article
- Review
- A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- CD80-Mediated T-Cell Suppression by Cancer Stem-like Cells in Head and Neck Squamous Cell Carcinoma.Cells · 2026Article
- Identification of Basement Membrane-Related Biomarkers in the Progression of Cutaneous Squamous Cell Carcinoma.International journal of molecular sciences · 2026Article
- Analysis of the relationship between serum LAMC2, TROAP and clinical stages and prognosis of non-muscle invasive bladder cancer.Open medicine (Warsaw, Poland) · 2026Article
- Single-cell transcriptomic profiling and machine learning identify S-nitrosylation-associated LAMC2 as a key prognostic driver in pancreatic cancer.Discover oncology · 2025Article
- LAMC2 promotes gallbladder carcinoma metastasis through the TGF-β pathway.Cancer cell international · 2025Article
- IGF2BP3 regulates EMP1 stability in an mCell death & disease · 2025Article
- Transgenerational diabetogenic effects of preconception exposure to inorganic arsenic in C57BL/6 mice are associated with dysregulation of DNA methylation and gene expression in G1 and G2 offspring.Archives of toxicology · 2025Article
- TGF-β1-mediated downregulation of L1CAM in pancreatic ductal adenocarcinoma drives upregulation of collagen 17A1 and MMP2, facilitating tumor invasiveness and metastasis.Cell death & disease · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- The role of LncRNA-MANCR induced by HIF-1α drive the malignant progression of pancreatic cancer by targeting miRNA-494/SIRT1 signaling axis under hypoxic conditions.Cancer gene therapy · 2025Article
- Deciphering the secrets of tumor-initiating cells in pancreatic ductal adenocarcinoma microenvironment: mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- NSUN2 Promotes Head and Neck Squamous Cell Carcinoma Progression by Targeting EMT-Related Gene LAMC2 in an mBiomedicines · 2024Article
- Galunisertib promotes bevacizumab-induced vascular normalization in nasopharyngeal carcinoma: Multi-parameter MRI evaluation.Molecular therapy. Oncology · 2024Article
- The disruption of NEAT1-miR-125b-5p-SLC1A5 cascade defines the oncogenicity and differential immune profile in head and neck squamous cell carcinoma.Cell death discovery · 2024Article
- Tumor Stroma as a Therapeutic Target for Pancreatic Ductal Adenocarcinoma.Biomolecules & therapeutics · 2024Review
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor-initiating cells (TIC), also known as cancer stem cells, are considered a specific subpopulation of cells necessary for cancer initiation and metastasis; however, the mechanisms by which they acquire metastatic traits are not well understood.
methodsLAMC2 transcriptional levels were evaluated using publicly available transcriptome data sets, and LAMC2 immunohistochemistry was performed using a tissue microarray composed of PDAC and normal pancreas tissues. Silencing and tracing of LAMC2 was performed using lentiviral shRNA constructs and CRISPR/Cas9-mediated homologous recombination, respectively. The contribution of LAMC2 to PDAC tumorigenicity was explored in vitro by tumor cell invasion, migration, sphere-forming and organoids assays, and in vivo by tumor growth and metastatic assays. mRNA sequencing was performed to identify key cellular pathways upregulated in LAMC2 expressing cells. Metastatic spreading induced by LAMC2- expressing cells was blocked by pharmacological inhibition of transforming growth factor beta (TGF-β) signaling.
resultsWe report a LAMC2-expressing cell population, which is endowed with enhanced self-renewal capacity, and is sufficient for tumor initiation and differentiation, and drives metastasis. mRNA profiling of these cells indicates a prominent squamous signature, and differentially activated pathways critical for tumor growth and metastasis, including deregulation of the TGF-β signaling pathway. Treatment with Vactosertib, a new small molecule inhibitor of the TGF-β type I receptor (activin receptor-like kinase-5, ALK5), completely abrogated lung metastasis, primarily originating from LAMC2-expressing cells.
conclusionsWe have identified a highly metastatic subpopulation of TICs marked by LAMC2. Strategies aimed at targeting the LAMC2 population may be effective in reducing tumor aggressiveness in PDAC patients. Our results prompt further study of this TIC population in pancreatic cancer and exploration as a potential therapeutic target and/or biomarker.
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