ArticleBiochemical pharmacology2013
Mesalamine modulates intercellular adhesion through inhibition of p-21 activated kinase-1.
Article in Biochemical pharmacology, 2013. 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, 50 citations in OpenAlex.
- An unexpected tumor-resistant phenotype from floxing PAK1 in a mouse model of colitis associated cancer.Scientific reports · 2025Article
- Mesalazine and Lactoferrin as Potential Adjuvant Therapy in Colorectal Cancer: Effects on Cell Viability and Wnt/β-Catenin Pathway.Current issues in molecular biology · 2025Article
- LC-MS/MS-based metabolomics and proteomics reveal the intervention of Kangnian decoction on the postoperative intestinal adhesion of rats.Frontiers in pharmacology · 2024Article
- Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer.Molecules (Basel, Switzerland) · 2023Review
- Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.Molecular cancer · 2022Review
- Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet?Toxins · 2021Review
- 5-Aminosalicylic acid inhibits stem cell function in human adenoma-derived cells: implications for chemoprophylaxis in colorectal tumorigenesis.British journal of cancer · 2021Article
- A Novel PAK1-Notch1 Axis Regulates Crypt Homeostasis in Intestinal Inflammation.Cellular and molecular gastroenterology and hepatology · 2021Article
- Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction.Bioscience reports · 2020Article
- Mesalamine and azathioprine modulate junctional complexes and restore epithelial barrier function in intestinal inflammation.Scientific reports · 2019Article
- p-21 Activated Kinase as a Molecular Target for Chemoprevention in Diabetes.Geriatrics (Basel, Switzerland) · 2018Review
- PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis.Nature communications · 2016Article
- The potential role of the NEK6, AURKA, AURKB, and PAK1 genes in adenomatous colorectal polyps and colorectal adenocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Article
- PAK1 modulates a PPARγ/NF-κB cascade in intestinal inflammation.Biochimica et biophysica acta · 2015Article
- Overexpression of PAK1 promotes cell survival in inflammatory bowel diseases and colitis-associated cancer.Inflammatory bowel diseases · 2015Article
- Five-aminosalicylic Acid: an update for the reappraisal of an old drug.Gastroenterology research and practice · 2015Review
- Chemoprevention of colorectal cancer.Digestive diseases (Basel, Switzerland) · 2015Review
- Republished: tracing PAKs from GI inflammation to cancer.Postgraduate medical journal · 2014Article
- P21-activated kinase in inflammatory and cardiovascular disease.Cellular signalling · 2014Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesalamine (5-ASA) is widely used for the treatment of ulcerative colitis, a remitting condition characterized by chronic inflammation of the colon. Knowledge about the molecular and cellular targets of 5-ASA is limited and a clear understanding of its activity in intestinal homeostasis and interference with neoplastic progression is lacking. We sought to identify molecular pathways interfered by 5-ASA, using CRC cell lines with different genetic background. Microarray was performed for gene expression profile of 5-ASA-treated and untreated cells (HCT116 and HT29). Filtering and analysis of data identified three oncogenic pathways interfered by 5-ASA: MAPK/ERK pathway, cell adhesion and β-catenin/Wnt signaling. PAK1 emerged as a consensus target of 5-ASA, orchestrating these pathways. We further investigated the effect of 5-ASA on cell adhesion. 5-ASA increased cell adhesion which was measured by cell adhesion assay and transcellular-resistance measurement. Moreover, 5-ASA treatment restored membranous expression of adhesion molecules E-cadherin and β-catenin. Role of PAK1 as a mediator of mesalamine activity was validated in vitro and in vivo. Inhibition of PAK1 by RNA interference also increased cell adhesion. PAK1 expression was elevated in APC(min) polyps and 5-ASA treatment reduced its expression. Our data demonstrates novel pharmacological mechanism of mesalamine in modulation of cell adhesion and role of PAK1 in APC(min) polyposis. We propose that inhibition of PAK1 expression by 5-ASA can impede with neoplastic progression in colorectal carcinogenesis. The mechanism of PAK1 inhibition and induction of membranous translocation of adhesion proteins by 5-ASA might be independent of its known anti-inflammatory action.
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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.