MMP2 modulates cell invasion in breast cancer cells
2018
Indian Association for the Cultivation of Science, Kolkata, India
Tumor cells are thought to secrete matrix metalloproteinases that degrade the extracellular matrix, promoting cell invasion. Some of these mechanisms have been elucidated in the last years, however, the role of TF-FVIIa/trypsin activation of protease-activated receptor 2 driving MMP2 upregulation in cell invasion is still unclear. Here, human breast cancer cells were used to study the different signalling mechanisms on the protease-activated receptor 2 mediated MMP2 increased expression that affect cell migration. The results showed that the knockdown of protease-activated receptor 2 hindered the upregulation of MMP2. Similarly, the knockdown of MMP2, impeded TF-FVIIa/trypsin-induced cell invasion. Moreover, the protease-activated receptor 2 driven upregulation of MMP2 was identified to lean on the PI3K-AKT-NF-ĸB pathway. Furthermore, TF, protease-activated receptor 2 and MMP2 were found to be overexpressed in invasive breast carcinoma tissues. Finally, the signalling axis triggered by MMP2 that modulates actin polymerization and cell migration was identified, which could be pharmacologically attenuated. Overall, the researchers describe the signalling pathway through which protease-activated receptor 2-induced MMP2 expression regulates cell invasion in breast cancer cells, which can help future developments of new therapeutical strategies to block metastatic processes.
Matrix metalloproteinase-2: A key regulator in coagulation proteases mediated human breast cancer progression through autocrine signaling
Prosenjit Sen
Added on: 10-30-2021
[1] https://www.sciencedirect.com/science/article/abs/pii/S0753332218333717[2] https://data.jrc.ec.europa.eu/dataset/ffebe454-ed9a-47cf-8a33-8cf70c1b7d38