ArticlePloS one2015
Slug-dependent upregulation of L1CAM is responsible for the increased invasion potential of pancreatic cancer cells following long-term 5-FU treatment.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Emerging Tumor Biomarkers in Pancreatic Cancer and Their Clinical Implications.Current issues in molecular biology · 2025Review
- Reshaping the Pancreatic Cancer Microenvironment at Different Stages with Chemotherapy.Cancers · 2023Review
- Targeting cancer stem cell plasticity in triple-negative breast cancer.Exploration of targeted anti-tumor therapy · 2023Review
- Immunotherapy and immunoengineering for breast cancer; a comprehensive insight into CAR-T cell therapy advancements, challenges and prospects.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Role of L1CAM in retinoblastoma tumorigenesis: identification of novel therapeutic targets.Molecular oncology · 2022Article
- Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.Nature communications · 2021Article
- Neuroglian regulates Drosophila intestinal stem cell proliferation through enhanced signaling via the epidermal growth factor receptor.Stem cell reports · 2021Article
- An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.Nature communications · 2021Article
- Different Shades of L1CAM in the Pathophysiology of Cancer Stem Cells.Journal of clinical medicine · 2020Review
- DNA methylation-driven EMT is a common mechanism of resistance to various therapeutic agents in cancer.Clinical epigenetics · 2020Article
- The Key Genes for Perineural Invasion in Pancreatic Ductal Adenocarcinoma Identified With Monte-Carlo Feature Selection Method.Frontiers in genetics · 2020Article
- Review
- L1CAM further stratifies endometrial carcinoma patients with no specific molecular risk profile.British journal of cancer · 2018Article
- 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin.Journal of experimental & clinical cancer research : CR · 2017Article
- L1 cell adhesion molecule (L1CAM) is a strong predictor for locoregional recurrences in cervical cancer.Oncotarget · 2017Article
- Article
- L1 increases adhesion-mediated proliferation and chemoresistance of retinoblastoma.Oncotarget · 2017Article
- TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling.Scientific reports · 2016Article
- Human papillomavirus oncoproteins differentially modulate epithelial-mesenchymal transition in 5-FU-resistant cervical cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic adenocarcinoma is a lethal disease with 5-year survival of less than 5%. 5-fluorouracil (5-FU) is a principal first-line therapy, but treatment only extends survival modestly and is seldom curative. Drug resistance and disease recurrence is typical and there is a pressing need to overcome this. To investigate acquired 5-FU resistance in pancreatic adenocarcinoma, we established chemoresistant monoclonal cell lines from the Panc 03.27 cell line by long-term exposure to increasing doses of 5-FU.
results5-FU-resistant cell lines exhibited increased expression of markers associated with multidrug resistance explaining their reduced sensitivity to 5-FU. In addition, 5-FU-resistant cell lines showed alterations typical for an epithelial-to-mesenchymal transition (EMT), including upregulation of mesenchymal markers and increased invasiveness. Microarray analysis revealed the L1CAM pathway as one of the most upregulated pathways in the chemoresistant clones, and a significant upregulation of L1CAM was seen on the RNA and protein level. In pancreatic cancer, expression of L1CAM is associated with a chemoresistant and migratory phenotype. Using esiRNA targeting L1CAM, or by blocking the extracellular part of L1CAM with antibodies, we show that the increased invasiveness observed in the chemoresistant cells functionally depends on L1CAM. Using esiRNA targeting β-catenin and/or Slug, we demonstrate that in the chemoresistant cell lines, L1CAM expression depends on Slug rather than β-catenin.
conclusionOur findings establish Slug-induced L1CAM expression as a mediator of a chemoresistant and migratory phenotype in pancreatic adenocarcinoma cells.
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