ArticleOncotarget2017
Tumor necrosis factor receptor 2/AKT and ERK signaling pathways contribute to the switch from fibroblasts to CAFs by progranulin in microenvironment of colorectal cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Expression of progranulin (GP88) protein appears as an independent prognostic factor for clinical progression in high-risk prostate cancer patients.Scientific reports · 2026Article
- CAF-derived exosomes: orchestrators of dysregulated signaling pathways in breast cancer progression.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Integration of scRNA-seq and bulk tissue RNA-seq data to identify cancer-associated fibroblast-related gene RGMA as a potential treatment target for esophageal cancer.Functional & integrative genomics · 2025Article
- Enhanced efficacy of dual chimeric antigen receptor-T cells targeting programmed death-ligand 1 and cancer-associated fibroblasts in colorectal cancerCytoJournal · 2025Article
- Progression of pulmonary arterial hypertension: A study in model.Open veterinary journal · 2024Article
- Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.Journal of experimental & clinical cancer research : CR · 2024Review
- Association between tumor necrosis factor receptor 2 and progression and poor prognosis of tumor stage 2‑3 esophageal squamous cell carcinoma and stratified analysis.Oncology letters · 2024Article
- Progranulin promoted the proliferation, metastasis, and suppressed apoptosis via JAK2-STAT3/4 signaling pathway in papillary thyroid carcinoma.Cancer cell international · 2023Article
- Progranulin Oncogenic Network in Solid Tumors.Cancers · 2023Review
- Anti-tumor necrosis factor-alpha monoclonal antibody suppresses colorectal cancer growth in an orthotopic transplant mouse model.PloS one · 2023Article
- Review
- Colon fibroblasts from Pirc rats (F344/NTac-ApcInternational journal of cancer · 2022Article
- RPP40 is a prognostic biomarker and correlated with tumor microenvironment in uterine corpus endometrial carcinoma.Frontiers in oncology · 2022Article
- Targeting TNFR2 in Cancer: All Roads Lead to Rome.Frontiers in immunology · 2022Review
- A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy.Translational cancer research · 2021Review
- The Role of Tumor Microenvironment Cells in Colorectal Cancer (CRC) Cachexia.International journal of molecular sciences · 2021Review
- Comprehensive Roles and Future Perspectives of Exosomes in Peritoneal Metastasis of Gastric Cancer.Frontiers in oncology · 2021Review
- The Role of Tumor Necrosis Factor in Manipulating the Immunological Response of Tumor Microenvironment.Frontiers in immunology · 2021Review
- Progranulin promotes diabetic fracture healing in mice with type 1 diabetes.Annals of the New York Academy of Sciences · 2020Article
- Role of cancer-associated fibroblasts in tumor structure, composition and the microenvironment in ovarian cancer.Oncology letters · 2019Review
Corrections and comments
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Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer associated fibroblasts (CAFs) are a crucial cellular component in tumor microenvironment and could promote tumor progression. CAFs are usually derived from resident fibroblasts, which undergoing an activated process stimulated by tumor cells. However, the agents and mechanism driving this switch have not yet been elucidated. Progranulin (PGRN), a well acknowledged secreted glycoprotein, could promote proliferation and angiogenesis of colorectal cancer (CRC) cells, and high expression of PGRN correlated with patient poor prognosis. Whether PGRN has effects on the function of stromal fibroblasts is unknown. Herein we found that there was a positive correlation between PGRN expression of CRC cells and expressions of smooth muscle actin α (α-SMA) on CAFs in CRC patient tissues. PGRN/α-SMA co-expression was positively correlated with CRC patient poor prognosis. Co-cultured with CRC cells or human recombinant PGRN (rPGRN), the expression of Ki67, fibroblast activation protein (FAP) and α-SMA in fibroblasts were all up-regulated significantly, accompanying with elevated cellular proliferation, migration and contraction. Whilst co-cultured with PGRN-silenced CRC cells, these functions were down-regulated. Studies of the underlying molecular mechanism demonstrated that either tumor necrosis factor receptor 2 (TNFR2)/Akt or the extracellular regulated kinase (ERK) signaling pathway contributed to modulate of Ki67, FAP, and α-SMA expression, and correlated to abilities of proliferation, migration and contraction in fibroblasts. In conclusion, PGRN plays an important role in activation of CRC fibroblasts, which may be taken as a prospective target of CRC therapy.
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