title: Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.
abstract: Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.
authors.affiliation: 1st Department of Propaedeutic Surgery, Hippocration General Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Linardoutsos
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Anastasios
authors.initials: A
authors.lastname: Machairas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Bramis
authors.forename: Georgios C
authors.initials: GC
authors.lastname: Zografos
mesh_terms: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000302:isolation & purification; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000473:pathology; D006801:Humans; D007610:Kallikreins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000302:isolation & purification
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D011956:Receptors, Cell Surface; D010447:Peptide Hydrolases; D007610:Kallikreins