ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Tissue Transglutaminase Mediated Tumor-Stroma Interaction Promotes Pancreatic Cancer Progression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 91 citations in OpenAlex.
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Biofabrication and artificial intelligence strategies for investigating solid- and fluid-pressure mechanobiology in pancreatic ductal adenocarcinoma.Cancer metastasis reviews · 2026Review
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells.European journal of medicinal chemistry · 2026Article
- Extracellular Matrix Signaling Cues: Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Stiff extracellular matrix activates the transcription factor ATF5 to promote the proliferation of cancer cells.iScience · 2025Article
- The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics.Cancer discovery · 2024Review
- Diagnostic efficiency of intravoxel incoherent motion-based virtual magnetic resonance elastography in pulmonary neoplasms.Cancer imaging : the official publication of the International Cancer Imaging Society · 2024Article
- Pirfenidone alleviates fibrosis by acting on tumour-stroma interplay in pancreatic cancer.British journal of cancer · 2024Article
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Preclinical evaluation of anEJNMMI radiopharmacy and chemistry · 2024Article
- The upregulation of TGM2 is associated with poor prognosis and the shaping of the inflammatory tumor microenvironment in lung squamous cell carcinoma.American journal of cancer research · 2024Article
- Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.Bioengineering (Basel, Switzerland) · 2023Article
- Correlating mechanical and gene expression data on the single cell level to investigate metastatic phenotypes.iScience · 2023Article
- Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Review
- Therapeutic Strategies to Overcome Fibrotic Barriers to Nanomedicine in the Pancreatic Tumor Microenvironment.Cancers · 2023Review
- The role of matrix stiffness in breast cancer progression: a review.Frontiers in oncology · 2023Review
- Article
- The Extracellular Matrix: A Key Accomplice of Cancer Stem Cell Migration, Metastasis Formation, and Drug Resistance in PDAC.Cancers · 2022Review
- Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAggressive pancreatic cancer is commonly associated with a dense desmoplastic stroma, which forms a protective niche for cancer cells. The objective of the study was to determine the functions of tissue transglutaminase (TG2), a Ca(2+)-dependent enzyme that cross-links proteins through transamidation and is abundantly expressed by pancreatic cancer cells in the pancreatic stroma. EXPERIMENTAL
designOrthotopic pancreatic xenografts and coculture systems tested the mechanisms by which the enzyme modulates tumor-stroma interactions.
resultsWe show that TG2 secreted by cancer cells effectively molds the stroma by cross-linking collagen, which, in turn, activates fibroblasts and stimulates their proliferation. The stiff fibrotic stromal reaction conveys mechanical cues to cancer cells, leading to activation of the YAP/TAZ transcription factors, promoting cell proliferation and tumor growth. Stable knockdown of TG2 in pancreatic cancer cells leads to decreased size of pancreatic xenografts.
conclusionsTaken together, our results demonstrate that TG2 secreted in the tumor microenvironment orchestrates the cross-talk between cancer cells and stroma fundamentally affecting tumor growth. Our study supports TG2 inhibition in the pancreatic stroma as a novel strategy to block pancreatic cancer progression.
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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.