Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

Kularathna, Pamuditha K.; Pagel, Charles N.; Mackie, Eleanor J.

doi:10.1016/j.biocel.2014.10.026

Cited by 11 publications

(10 citation statements)

References 87 publications

(109 reference statements)

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“…Protease activated receptor 2 ( PAR-2 ), also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1), is a transmembrane G-protein coupled receptor, belonging to the PAR family [8]. PAR-2 can be activated by trypsin, coagulation factors tryptase and matriptase [9,10].…”

Section: Introductionmentioning

confidence: 99%

PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

Tang

Han-Ying

et al. 2019

Bioscience Reports

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Objective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism. Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression. Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation. Conclusion: PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.

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Section: Introductionmentioning

confidence: 99%

PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

Tang

Han-Ying

et al. 2019

Bioscience Reports

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“…There is emerging information on the overlap between the neurobiology of cancer and pain. 26,27 Tumours causing severe pain may be more likely to metastasize strating that pain appears to enhance metastasis. 28,29 Regardless of the reason(s) how and why baseline pain might be associated with improved survival in dogs receiving combinatorial chemoradiotherapy, this finding provides some guidance as to which dogs might benefit most from the expense of SRT, rather than CHRT.…”

Section: Discussionmentioning

confidence: 99%

“…Another possible explanation we propose is that high pain could be an indicator of a more biologically aggressive tumour phenotype. There is emerging information on the overlap between the neurobiology of cancer and pain 26,27 . Tumours causing severe pain may be more likely to metastasize sooner than tumours characterized by low pain.…”

Section: Discussionmentioning

confidence: 99%

“…These SRT protocols utilize extreme hypofractionation (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Gy per fraction). 4,5 Initial reports indicate that when such radiotherapy is combined with systemically administered chemotherapy, overall survival is similar to that achieved when chemotherapy is combined with surgery (either limb amputation or limb-salvage surgery).…”

Section: Introductionmentioning

confidence: 99%

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Impact of radiation dose and pre‐treatment pain levels on survival in dogs undergoing radiotherapy with or without chemotherapy for presumed extremity osteosarcoma

Nolan

Green

DiVito

et al. 2020

Vet Comparative Oncology

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“…Protumorigenic activities attributed to PAR-2 signaling include chemokinesis, cell proliferation, invasion and migration, inflammatory signaling, and increased angiogenesis ( Fig. 1) in several tumor types including breast, oral, renal, pancreatic, gastric, lung, and esophageal cancers (36)(37)(38)(39)…”

Section: Par-2 Signaling and Cancermentioning

confidence: 99%

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

2019

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Pericellular proteolysis provides a significant advantage to developing tumors through the ability to remodel the extracellular matrix, promote cell invasion and migration, and facilitate angiogenesis. Recent advances demonstrate that pericellular proteases can also communicate directly to cells by activation of a unique group of transmembrane G-protein-coupled receptors (GPCR) known as proteaseactivated receptors (PAR). In this review, we discuss the specific roles of one of four mammalian PARs, namely PAR-2, which is overexpressed in advanced stage tumors and is activated by trypsin-like serine proteases that are highly expressed or otherwise dysregulated in many cancers. We highlight recent insights into the ability of different protease agonists to bias PAR-2 signaling and the newly emerging evidence for an interplay between PAR-2 and membrane-anchored serine proteases, which may co-conspire to promote tumor progression and metastasis. Interfering with these pathways might provide unique opportunities for the development of new mechanism-based strategies for the treatment of advanced and metastatic cancers.

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Tumour progression and cancer-induced pain: A role for protease-activated receptor-2?

Cited by 11 publications

References 87 publications

PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

Impact of radiation dose and pre‐treatment pain levels on survival in dogs undergoing radiotherapy with or without chemotherapy for presumed extremity osteosarcoma

Membrane-Anchored Serine Proteases and Protease-Activated Receptor-2–Mediated Signaling: Co-Conspirators in Cancer Progression

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