Intracellular signaling by cathepsin X: molecular mechanisms and diagnostic and therapeutic opportunities in cancer.
Cathepsin X is a cysteine carboxypeptidase, localized predominantly in immune cells, regulating their proliferation, maturation, migration and adhesion. It has recently been confirmed as a significant promoter of malignant progression. Its role in signal transduction was first implied through the interaction with integrin receptors, either by binding with the RGD motif or by proteolytic cleavage of the C-terminal amino acids of the cytosolic part of the integrin beta chain. Several other molecules, involved in cellular signaling, have since been shown to be targets for cathepsin X, such as γ-enolase, chemokine CXCL-12, bradykinin, kallidin, huntingtin and profilin 1. In cancer, cathepsin X regulates adhesion of tumor and endothelial cells and their migration and invasion through the extracellular matrix. It also promotes tumor progression by bypassing cellular senescence and by inducing an epithelial-mesenchymal transition. The high RNA and protein levels of cathepsin X, found in tumor samples and bodily fluids of patients with various cancer types, further support its active role in tumor progression. Its prognostic value and relation to response to chemotherapy confirm cathepsin X as a new target for improving diagnosis and treating cancer patients.
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia; Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia. Electronic address: janko.kos@ffa.uni-lj.si.
Janko
J
Kos
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Tjaša
T
Vižin
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Urša Pečar
UP
Fonović
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Anja
A
Pišlar
D056657:Cathepsin K / Q000378:metabolism*; D002448:Cell Adhesion; D042783:Endothelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D042541:Intracellular Space / Q000201:enzymology*; D008954:Models, Biological; D009369:Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000628:therapy; D015398:Signal Transduction
D039641:Integrin beta Chains; D056657:Cathepsin K
Adhesion; Cancer; Cathepsin X; Migration; Signaling