KLK6 protease accelerates skin tumor formation and progression

Area of Science:

• Oncology
• Dermatology
• Biochemistry

Background:

• Kallikrein-related peptidase 6 (KLK6) is a serine protease implicated in various cancers.
• KLK6's role in non-melanoma skin cancer and its specific function in skin tumorigenesis remain uninvestigated.
• KLK6 is known to be active in the epidermis and associated with normal skin differentiation.

Purpose of the Study:

• To investigate the role of KLK6 in skin tumorigenesis in vivo.
• To determine if KLK6 is implicated in the development and progression of skin cancer.

Main Methods:

• Carcinogenesis was induced in Klk6-/- mice using 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol 13-acetate (DMBA/TPA).
• Multistage skin tumor development and progression were monitored.
• Histological analyses and assessment of tumor formation by implanted skin cancer cells were performed.

Main Results:

• Klk6-/- and Klk6+/- mice exhibited significant resistance to tumor growth and development compared to wild-type (wt) mice.
• Tumors in Klk6-/- mice were predominantly benign papillomas, while wt mice developed squamous cell carcinomas (SCCs).
• KLK6 deficiency attenuated inflammation in response to TPA and reduced the formation of tumors from implanted cancer cells.

Conclusions:

• KLK6 acts as a novel tumor-promoting factor in early skin cancer.
• KLK6 is identified as a crucial molecular link between skin inflammation and tumor-promoting inflammatory processes.
• Targeting KLK6 may offer a therapeutic strategy for non-melanoma skin cancer.