The unknown caspase: The role of caspase-14 in cell death and disease

Abstract

Caspase-14 is unique among caspase family proteases. It is the shortest member of the caspase family that was first described as a developmentally regulated protease due to its high expression in embryonic tissues. Based on its pathophysiological functions, Caspase-14 cannot be categorized into any of the three caspase groups: cytokine activators, initiator or executioner caspases. Unlike the rest of the family members, it is not proteolytically processed at Asp residue. Its proteolytic processing between 152Ile and 153Lys has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. However, emerging evidence highlight the role of Caspase-14 in cell death and its implication in disease. Caspase-14 has been reported to inhibit apoptosis in certain cancer cells and to increase their resistance to chemotherapeutic drugs. Its expression has also been found to be differentially regulated in tumors and to correlate with specific subsets of epithelial cancers with distinct clinical behaviors. It is therefore becoming increasingly evident that this unique Caspase, whose functions are primarily unknown, may play a role in disease progression and carcinogenesis. This review will bring forth the information that has accumulated since the discovery of Caspase-14 almost 20 years ago, and explore its role in cell death and disease with special emphasis on its implication in cancer. © 2016 by Nova Science Publishers, Inc.