TMPRSS2 is an androgen-regulated cell surface serine protease expressed predominantly in prostate epithelium. TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastasis. Through the generation of mouse models with a targeted deletion of Tmprss2, we demonstrate that the activity of this protease regulates cancer cell invasion and metastasis to distant organs. By screening combinatorial peptide libraries we identified a spectrum of TMPRSS2 substrates that include pro-hepatocyte growth factor (HGF). HGF activated by TMPRSS2 promoted c-Met receptor tyrosine kinase signaling, and initiated a pro-invasive EMT phenotype. Chemical library screens identified a potent bioavailable TMPRSS2 inhibitor that suppressed prostate cancer metastasis in vivo. Together, these findings provide a mechanistic link between androgen-regulated signaling programs and prostate cancer metastasis that operate via context-dependent interactions with extracellular constituents of the tumor microenvironment.
Bromhexine is derived from the Adhatoda vasica plant and aids in the clearance of excess mucus, improving breathing and reducing cough. It was introduced into the market in 1963, and is widely available as an over-the-counter drug in many countries. Recently, bromhexine and its metabolite ambroxol have garnered interest for the potential prevention and treatment of COVID-19 due to their interactions with cell receptors in the lungs.
Nice one, thank you!
A point made by Jcancom, on this line, in one of his comments here in the context of prostate cancer https://www.cancertreatmentsresearch.com/prostate-cancer/#comment-6008 and by myself ere in the context of COVID-19 https://www.cancertreatmentsresearch.com/a-list-of-drugs-and-supplement-to-fight-coronavirus/?highlight=TMPRSS2
Nice to know Bromhexine acts along this line.
Kind regards,
Daniel
Thanks Danie;
I think an important point is that bromhexine is a mucolytic drug. Mucolytics reduce mucus viscosity. Diverse human malignancies overexpress transmembrane mucins to exploit their role in signalling cell growth and survival. Mucins have been identified as markers of adverse prognosis. Certain transmembrane mucins induce transformation and promote tumour progression and are associated with chemoresistance and metastasis. Therefore mucin is an attractive therapeutic target.
