Cathepsin V plays a crucial role in the metastasis and growth of lung cancer

Abstract Cathepsin V (CTSV) is a cysteine cathepsin protease located in lysosome and plays crucial role in extracellular matrix degradation. It is reported that CTSVis correlated with poor prognosis with multiple cancers, but the underlying mechanism remains unclear. In this study, we aimed to clarify the molecular mechanism of how CTSV functions in lung cancer. Here, we identified that CTSV is upregulated in high metastatic property lung cancer cells. Depletion of CTSV inhibited the metastasis and growth of lung cancer. Mechanistic studies showed that CTSV functions by cleaving fibronectin, E-cadherin and N-cadherin and remodeling the extracellular matrix (ECM) of lung cancer. Our data showed that CTSV is an essential component of lysosome, reduction of CTSV increased pH value of lysosome and led to lysosome dysfunction. Together, our findings reveal a molecular mechanism of how CTSV drive metastasis and growth of lung cancer, suggesting that CTSV-targeting approach is a promising strategy for lung cancer.