Testes-specific
protease 50 (TSP50) has
threonine activity and has homology to
serine proteases. TSP50
protein, which is encoded by a possible proto-oncogene, is overexpressed in cervical
tumor tissues. Through overexpression experiments using both TSP50 and a TSP50 mutant (TSP50 T310A), it is clear that this
protein may play an important role in
carcinogenesis and progression of cervical
tumor. However, the mechanism underlying how TSP50 modulates
cancer cell growth is still unclear. To examine the difference in TSP50 expression in cervical
carcinoma tissues and in paracarcinoma tissues, we detected TSP50
mRNA and
protein in ten paired tissues from patients with
cervical cancer. To determine whether TSP50's
threonine protease activity is crucial for its effects on
tumor formation, we generated a mutant version of TSP50 (T310A). Via overexpression and silencing experiments, we identified a role for TSP50 in cell proliferation and migration. Furthermore, we examined the signaling pathway of TNF-α-induced NFκB activation to explain the mechanism by which TSP50 participates in
tumorigenesis. Similarly, we found that all these effects could be abolished by the TSP50 T310A mutation. Our results suggest that the
threonine 310 residue within TSP50 helps modulate its role in cervical
tumorigenesis and indicates that TSP50's role in
tumorigenesis may be dependent on its interaction with TNF-α-induced NF-κB.