» Articles » PMID: 22848234

Protease-activated Receptors in Cancer: A Systematic Review

Overview
Journal Oncol Lett
Specialty Oncology
Date 2012 Aug 1
PMID 22848234
Citations 23
Authors
Affiliations
Soon will be listed here.
Abstract

The traditional view of the role of proteases in tumor growth, progression and metastasis has significantly changed. Apart from their contribution to cancer progression, it is evident that a subclass of proteases, such as thrombin, serves as signal molecules controlling cell functions through the protease-activated receptors (PARs). Among the four types of PAR (PAR1-4; cloned and named in order of their discovery), PAR1, PAR3 and PAR4 are activated by thrombin, unlike PAR2, which is activated by trypsin-like serine proteases. Thrombin has been proven to be a significant factor in both the behavior of cancer in its involvement in hemostasis and blood coagulation. Thrombin is a key supporter of various cellular effects relevant to tumor growth and metastasis, as well as a potent activator of angiogenesis, which is essential for the growth and development of all solid tumor types. This review presents an overview of the role of PAR-mediated thrombin in angiogenesis and cancer, focusing on the ability of PAR1- and PAR4-mediated thrombin to affect tumorigenesis and angiogenesis.

Citing Articles

PAR2 activation on human tubular epithelial cells engages converging signaling pathways to induce an inflammatory and fibrotic milieu.

Vesey D, Iyer A, Owen E, Kamato D, Johnson D, Gobe G Front Pharmacol. 2024; 15:1382094.

PMID: 39005931 PMC: 11239397. DOI: 10.3389/fphar.2024.1382094.


Cancer progression and tumor hypercoagulability: a platelet perspective.

Zhang Y, Zeng J, Bao S, Zhang B, Li X, Wang H J Thromb Thrombolysis. 2024; 57(6):959-972.

PMID: 38760535 DOI: 10.1007/s11239-024-02993-0.


Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy.

Paul S, Mukherjee T, Das K Cancers (Basel). 2024; 16(8).

PMID: 38672649 PMC: 11048528. DOI: 10.3390/cancers16081568.


Anti-Inflammatory and Anticancer Effects of Anticoagulant Therapy in Patients with Malignancy.

Russo V, Falco L, Tessitore V, Mauriello A, Catapano D, Napolitano N Life (Basel). 2023; 13(9).

PMID: 37763292 PMC: 10532829. DOI: 10.3390/life13091888.


Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.

Pierce D, Buchanan F, Macrae F, Mills J, Cox A, Abualsaoud K PLoS Pathog. 2023; 19(7):e1011529.

PMID: 37478143 PMC: 10395923. DOI: 10.1371/journal.ppat.1011529.


References
1.
Bromberg M, Bailly M, Konigsberg W . Role of protease-activated receptor 1 in tumor metastasis promoted by tissue factor. Thromb Haemost. 2002; 86(5):1210-4. View

2.
Miyata S, Koshikawa N, Yasumitsu H, Miyazaki K . Trypsin stimulates integrin alpha(5)beta(1)-dependent adhesion to fibronectin and proliferation of human gastric carcinoma cells through activation of proteinase-activated receptor-2. J Biol Chem. 2000; 275(7):4592-8. DOI: 10.1074/jbc.275.7.4592. View

3.
Derian C, Damiano B, Addo M, Darrow A, DAndrea M, Nedelman M . Blockade of the thrombin receptor protease-activated receptor-1 with a small-molecule antagonist prevents thrombus formation and vascular occlusion in nonhuman primates. J Pharmacol Exp Ther. 2003; 304(2):855-61. DOI: 10.1124/jpet.102.042663. View

4.
Palumbo J, Degen J . Hemostatic factors in tumor biology. J Pediatr Hematol Oncol. 2000; 22(3):281-7. DOI: 10.1097/00043426-200005000-00019. View

5.
Macfarlane S, Seatter M, Kanke T, HUNTER G, Plevin R . Proteinase-activated receptors. Pharmacol Rev. 2001; 53(2):245-82. View