ArticlePloS one2015
Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.
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 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- GPCRs interaction with LGR5: Implications to cancer stemness.Journal of Cancer · 2026Article
- To generate functional anti-protease-activated receptor-4 (PAR4), a G protein-coupled receptor, antibodies through PAR4-mRNA-LNP immunization.NPJ vaccines · 2025Article
- PARInternational journal of molecular sciences · 2025Article
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- The expression of trefoil factor family member 2 in increased at an acidic pH.Oncology letters · 2024Article
- Expression profiling of anticancer genes in colorectal cancer patients and their in vitro induction by riproximin, a ribosomal inactivating plant protein.Journal of cancer research and clinical oncology · 2023Article
- PARs in the inflammation-cancer transformation of CRC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells.Cell communication and signaling : CCS · 2020Article
- Using PAR4 Inhibition as an Anti-Thrombotic Approach: Why, How, and When?International journal of molecular sciences · 2019Review
- Transcriptional Landscape of PARs in Epithelial Malignancies.International journal of molecular sciences · 2018Review
- PAR4 overexpression promotes colorectal cancer cell proliferation and migration.Oncology letters · 2018Article
- Opposite response to hypoxia by breast cancer cells between cell proliferation and cell migration: A clue from microRNA expression profile.Oncology letters · 2018Article
- Activation of PAR4 Upregulates p16 through Inhibition of DNMT1 and HDAC2 Expression via MAPK Signals in Esophageal Squamous Cell Carcinoma Cells.Journal of immunology research · 2018Article
- Aberrantly Expressed Genes and miRNAs in Slow Transit Constipation Based on RNA-Seq Analysis.BioMed research international · 2018Article
- Contributions of Protease-Activated Receptors PAR1 and PAR4 to Thrombin-Induced GPIIbIIIa Activation in Human Platelets.Molecular pharmacology · 2017Article
- Heat shock factor 2 is associated with the occurrence of lung cancer by enhancing the expression of heat shock proteins.Oncology letters · 2016Article
- Trefoil factor family 2 expression inhibits gastric cancer cell growth and invasion in vitro via interactions with the transcription factor Sp3.International journal of molecular medicine · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protease-activated receptor 4 (PAR4), a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2), a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38), western blotting (n=38) and tissue microarrays (n = 66). The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the functions and molecular mechanisms of Proteinase-activated receptors (PARs) and Trefoil factor factors (TFFs) during the progression of colorectal cancer.
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