CTSG restraines the proliferation and metastasis of head and neck squamous cell carcinoma by blocking the JAK2/STAT3 pathway

Background

Head and neck squamous cell carcinoma (HNSC) is recognized as the sixth most prevalent cancer globally, with around 900,000 new cases diagnosed each year. The management of HNSC poses significant challenges due to its rising incidence and suboptimal treatment outcomes in many patients. Thus, understanding the underlying molecular mechanisms that drive the onset and advancement of HNSC is crucial in order to steer the creation of novel treatment strategies. Previous researches have suggested that Cathepsin G (CTSG), a serine protease, may play a role in tumorigenesis, but its exact function in HNSC is still unknown.

Methods

The TCGA and GTEx datasets were utilized to examine the expression and potential role of CTSG in pancancer. CTSG expression in HNSC tissues and normal tissues was analyzed using qRT-PCR, Western blot and immunohistochemistry techniques. The effects of altering CTSG expression on proliferation, migration, and apoptosis of HNSC cells were evaluated using various tests such as MTT assays, colony formation assays, wound-healing assays, transwell assays, flow cytometry, and xenograft tumor growth models. The functionality of CTSG on the JAK2/STAT3 pathway was validated using activators and inhibitors of this pathway after comfirming that CTSG could regulate this pathway.

Results

In our study, we indicated that CTSG expression in HNSC tumor tissues was significantly lower than in adjacent normal tissues and CTSG gene level was positively correlated with patient prognosis. Additionally, we observed a decrease in tumor proliferation and migration, as well as an increase in apoptosis, following CTSG overexpression. Conversely, opposite effects were noted upon CTSG knockdown. Mechanistically, CTSG overexpression inhibited JAK2/STAT3 signaling, while CTSG knockdown activated it. This was confirmed by using IL-6 and JAK2 inhibitor.

Conclusion

CTSG impedes the proliferation and metastasis of HNSC in vivo and in vitro. CTSG is potential to act as a cancer suppressor in HNSC by focusing on the JAK2/STAT3 signaling pathway, indicating its possible use as a diagnostic marker and treatment target for HNSC.