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Cystatin A Down-regulation in Head and Neck Squamous Cell Carcinoma Cell Lines Decreases Cancer Hallmark SignaturesFunding This work was supported by PGIMER Special Research Grant for funding the study and Council for Scientific and Industrial Research (CSIR), New Delhi, for providing the fellowship to AC.
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.
Ethics Approval Statement
This study was performed after getting the approval of the Institute Ethics Committee, PGIMER, Chandigarh.
Data Availability Statement
Detailed data and protocols shall be made available by the corresponding author on reasoned request.
G.S.B., A.C., and A.P. conceived and planned the experiments. G.S.B. carried out the experiments. G.S.B. wrote the manuscript with input from all authors. A.B. analyzed the IHC and ICC slides. G.S.B., A.C., A.B, R.K.V., and A.P. contributed to the analysis and interpretation of the results. A.C. and A.P. edited the manuscript
Article published online:
21 August 2023
© 2023. National Academy of Medical Sciences (India). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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