ArticleGastroenterology2022
Mucin 5AC-Mediated CD44/ITGB1 Clustering Mobilizes Adipose-Derived Mesenchymal Stem Cells to Modulate Pancreatic Cancer Stromal Heterogeneity.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting Oncomucin-Driven Immunosuppression Improves the Efficacy of K-rasGastroenterology · 2026Article
- Unique N-glycoproteomics and phosphoproteomics of mucins predict clinical outcomes in pancreatic ductal adenocarcinoma.Cancer letters · 2026Article
- Targeting Interactions Between Siglec-10 and α3β1 Integrin Enhances Macrophage-Mediated Phagocytosis of Pancreatic Cancer.Cancer research · 2026Article
- Beyond cardiac fibroblasts: research advances on understanding and targeting intercellular communication networks in cardiac fibrosis.Frontiers in cardiovascular medicine · 2026Review
- Mucin 5ac modulates cancer-associated fibroblast heterogeneity through epigenetic reprogramming of precursor cells.American journal of physiology. Cell physiology · 2026Article
- Identification of a migrasome-related lncRNA signature and its prognostic and immunological role in bladder cancer.Frontiers in immunology · 2026Article
- Mechanistic Foundations of KRAS-Driven Tumor Ecosystems: Integrating Crosstalk among Immune, Metabolic, Microbial, and Stromal Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Emerging pathways yielding opportunities for future treatments in pancreatic ductal adenocarcinoma.Expert opinion on therapeutic targets · 2025Review
- HAMA-SBMA hydrogel with anti-inflammatory properties delivers cartilage organoids, boosting cartilage regeneration.Journal of nanobiotechnology · 2025Article
- A machine learning-based prognostic signature utilizing MSC proteomics for predicting bladder cancer prognosis and treatment response.Translational oncology · 2025Article
- CircRNF13 enhances IGF2BP1 phase separation-mediated ITGB1 mRNA stabilization in an m6A-dependent manner to promote oral cancer cisplatin chemoresistance.Molecular cancer · 2025Article
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.International journal of molecular sciences · 2024Article
- Potential Consequences of the Use of Adipose-Derived Stem Cells in the Treatment of Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Multidimensional screening of pancreatic cancer spheroids reveals vulnerabilities in mitotic and cell-matrix adhesion signaling that associate with metastatic progression and decreased patient survival.Biochemical and biophysical research communications · 2024Article
- The characteristics and the multiple functions of integrin β1 in human cancers.Journal of translational medicine · 2023Review
- Epigenetic regulation of cancer-associated fibroblast heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- RAD-TGTs: high-throughput measurement of cellular mechanotype via rupture and delivery of DNA tension probes.Nature communications · 2023Article
- CD248 promotes migration and metastasis of osteosarcoma through ITGB1-mediated FAK-paxillin pathway activation.BMC cancer · 2023Article
- Mesenchymal Stromal Cell-Based Targeted Therapy Pancreatic Cancer: Progress and Challenges.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsSecreted mucin 5AC (MUC5AC) promotes pancreatic cancer (PC) progression and chemoresistance, suggesting its clinical association with poor prognosis. RNA sequencing analysis from the autochthonous pancreatic tumors showed a significant stromal alteration on genetic ablation of Muc5ac. Previously, depletion or targeting the stromal fibroblasts showed an ambiguous effect on PC pathogenesis. Hence, identifying the molecular players and mechanisms driving fibroblast heterogeneity is critical for improved clinical outcomes.
methodsAutochthonous murine models of PC (Kras
resultsThe KCM tumors showed a significant decrease in the expression of α-smooth muscle actin and fibronectin compared with histology-matched KC tumors. Our study showed that MUC5AC, carrying tumor secretome, gets enriched in the adipose tissues of tumor-bearing mice and patients with PC, promoting CD44/CD29 (integrin-β1) clustering that leads to Rac1 activation and migration of AD-MSCs. Furthermore, treatment with KC-derived serum enhanced proliferation and migration of AD-MSCs, which was abolished on Muc5ac-depletion or pharmacologic inhibition of CXCR2 and Rac1, respectively. The AD-MSCs significantly contribute toward α-smooth muscle actin-positive cancer-associated fibroblasts population in Muc5ac-dependent manner, as suggested by autochthonous tumors, co-implantation xenografts, and patient tumors.
conclusionMUC5AC, secreted during PC progression, enriches in adipose and enhances the mobilization of AD-MSCs. On recruitment to pancreatic tumors, AD-MSCs proliferate and contribute towards stromal heterogeneity.
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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.