Affiliation:
1. Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2. Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3. Department of ENT, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Abstract
Abstract
Background Cystatin A (CSTA), an endogenous inhibitor of lysosomal cysteine protease, is expressed primarily in epithelial tissues. The expression of CSTA was found to be dysregulated in various cancers and associated with cancer pathogenesis, but its role is reported to be contradictory. Our previous preliminary study found CSTA to be upregulated in the saliva and tissues of patients with head and neck squamous cell carcinoma (HNSCC). In this current study, we have explored the role of CSTA in the pathophysiology of HNSCC.
Methods First, we confirmed the upregulation of CSTA in CAL 27 (p = 0.0242) and FaDu (p = 0.0014), two HNSCC cell lines, compared to the normal gingival epithelium. CSTA was then stably knocked down in CAL 27 and FaDu using the lentiviral short hairpin RNA pLKO vector transduction to study the effects of CSTA knockdown on various cancer hallmarks such as cell proliferation ability, invasion, migration, colony formation, and chemotherapy-induced apoptosis.
Results CSTA knockdown significantly decreased cell viability, cell migration, transwell invasion, and colony formation in both cell lines. CSTA downregulation also enhanced cisplatin-induced apoptosis.
Conclusion Overall, this study suggests the protumorigenic role of CSTA in HNSCC.