Abstract
TMPRSS2 is an androgen-regulated cell-surface serine protease expressed predominantly in prostate epithelium that is involved in the viral entry and spread of COVID-19.
TMPRSS2 is expressed highly in localized high-grade prostate cancers and in the majority of human prostate cancer metastases. 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 proinvasive epithelial-to-mesenchymal transition 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.
Significance
The vast majority of prostate cancer deaths are due to metastasis. Loss of TMPRSS2 activity dramatically attenuated the metastatic phenotype through mechanisms involving the HGF-c-MET axis. Therapeutic approaches directed toward inhibiting TMPRSS2 may reduce the incidence or progression of metastasis in patients with prostate cancer.
radiation treatments led to perforated colon?
Radiation Treatment Decision
Syncromune Granted FDA Fast-Track Designation for SYNC-T SV-102 for the Treatment of Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
The continuing saga of Scout and Coco, Not all change is welcome. 
My 80 year-old dad with MPCa, broke his leg and now seems to be giving up. Advice on best anti-anxiety meds desperately needed.
