KLK5 and KLK7 drive cervical carcinoma via KLK14-dependent RhoA and NF-κB pathways

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Human Papillomavirus (HPV) infection affects 12% globally, a primary cause of cervical cancer.
• HPV is a key driver of cervical cancer, but its precise carcinogenic mechanisms are not fully understood.

Purpose of the Study:

• Investigate the role of serine proteases in HPV-mediated cervical carcinogenesis.
• Elucidate the contribution of specific serine proteases and their inhibitors to cervical cancer development.

Main Methods:

• Analyzed human biopsies for serine protease expression (matriptase, KLK5, KLK7) and inhibitors.
• Utilized genetically engineered mice, bulk RNA-seq, and reporter assays for mechanistic studies.
• Examined the role of these proteases in HPV-dependent cervical carcinogenesis.

Main Results:

• Increased expression of matriptase, KLK5, and KLK7 observed in early cervical carcinogenesis.
• Absence of KLK5 and KLK7 reduced HPV-dependent phenotype by modulating KLK14 activation.
• KLK14 demonstrated a pro-tumorigenic effect via PAR-2-dependent RhoA and NF-κB signaling.

Conclusions:

• Serine proteases KLK5, KLK7, and KLK14 are critical in cervical carcinogenesis.
• These proteases represent promising therapeutic targets for cervical cancer treatment.
• Understanding these mechanisms may lead to novel therapeutic strategies.