Complement components C1r and C1s promote oral squamous cell carcinoma cell proliferation

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Oral squamous cell carcinoma (OSCC) is the most common oral cancer, originating from mucosal or odontogenic epithelium.
• Gene expression analysis revealed elevated "COMPLEMENT" gene sets in OSCC lesions.
• The role of the complement system in OSCC tumorigenesis is not well understood.

Purpose of the Study:

• To investigate the involvement of complement components in the development of oral squamous cell carcinoma (OSCC).
• To explore the relationship between complement system activation and OSCC cell proliferation and signaling pathways.

Main Methods:

• Utilized siRNA and shRNA to assess OSCC cell proliferation in vitro and in vivo.
• Employed western blotting to analyze intracellular signaling pathway activation.
• Investigated C1s expression in OSCC tissues via immunohistochemistry and assessed the impact of MEK1/2 inhibition.

Main Results:

• C1r/C1s expression positively regulated ERK and AKT activation, promoting OSCC cell growth.
• A negative feedback loop was identified where activated ERK controlled C1r/C1s expression.
• High C1s expression in OSCC tumors correlated with elevated phosphorylated ERK and Ki-67 levels.

Conclusions:

• The complement system, particularly C1r/C1s, appears to be a common molecular mechanism in OSCC tumorigenesis from diverse epithelial origins.
• Elevated C1r/C1s expression significantly contributes to oral squamous cell carcinoma cell proliferation.