Hgf Activators Enhance The Spread Of Tumours

HGFA and matriptase are responsible for the activation of HGF in tumours, which suggests that these proteases will aid the growth and motility of cancer cells, particularly carcinomas, and further enhance vascularisation of tumours. Matriptase also activates latent urokinase-type plasminogen activator, which subsequently activates plasmin (88). This cascade results in the activation of plasmin, and the coactivation of matrix metalloproteases, which leads to the degradation of ECM components and further enhances tumour cell invasion, extravasation and metastasis (136). Therefore, increased HGFA and matriptase activity may therefore correlate with enhanced metastatic potential of tumours.

A balance between protease activity and protease inhibition is crucial for maintaining normal cell function. The balance between proteases and their inhibitors is disrupted in cancer cells, and this shift in regulation can lead to the progression of tumour cells (137, 138). Therefore, the balance between HGF activation and HGF activation suppression is the crucial step controlling the metastatic influence of HGF. Overexpression of HGFA and/or matriptase may disrupt the activator/inhibitor ratio in favour of increased HGF activation, resulting in an increase in HGF activity, and subsequently enhancing the metastatic stimulus.

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