Disease relevance of KLK7

• Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers [1].
• KLK7 status also correlated with size of residual tumor postsurgery [2].
• This subgroup was least influenced by postoperative treatment and thus best showed the impact of KLK7 expression on the natural course of breast cancer disease [3].
• KLK5 expression is significantly more expressed in squamous cell carcinoma than in matched nonmalignant lung tissue (P=0.02), whereas expression of KLK7 was decreased in adenocarcinoma (P=0.003) [4].
• KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer [4].

High impact information on KLK7

• Two members of the human tissue kallikrein (KLK) family of (chymo)tryptic-like serine proteases, KLK5 and KLK7, are implicated in desquamation by digestion of (corneo)desmosomes and inhibition by desquamation-related serine protease inhibitors (SPIs) [5].
• The extended substrate specificity profiles are in good agreement with known substrate cleavage sites but also in accord with experimentally solved (hK4, hK6, and hK7) or modeled structures [6].
• The stratum corneum chymotryptic enzyme (SCCE) has been previously purified from human stratum corneum and resembles a chymotryptic serine endopeptidase involved in physiological detachment of corneocytes from human stratum corneum [7].
• Thus, antileukoprotease, which is known to be produced by human keratinocytes, is likely to be the major physiological inhibitor of SCCE in the epidermis [7].
• Tryptic digestion removed this propeptide and yielded a proteolytically active protein with the same NH2-terminal amino acid sequence as native SCCE [8].

Chemical compound and disease context of KLK7

• KLK7 gene expression was significantly lower in breast cancer patients of low stage (I/II) (p = 0.011) and patients with positive progesterone receptors (p = 0.022) [9].

Biological context of KLK7

• KLK7 is composed of five coding exons which have similar lengths to exons of other kallikrein-like genes [10].
• Altogether, our results suggest that variability in KLK5 and KLK7 gene expression might be involved in lung tumorigenesis and useful for clinical purposes [4].
• Recombinant SCCE was found to be heterogenous regarding glycosylation in a manner similar to that of the native enzyme [8].
• Our data suggest that hK7 protein overexpression is associated with a more aggressive phenotype in brain cancer cells [11].
• Skin barrier function can be impaired first by a genetic predisposition to produce increased levels of stratum corneum chymotryptic enzyme [12].

Anatomical context of KLK7

• We here provide evidence that KLK7 is also expressed at relatively high levels in the central nervous system, kidney, mammary and salivary glands [10].
• LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum [13].
• In the trans-Golgi network (TGN), bulbous protrusions containing GlcCer, Cdsn, KLK7 and KLK8, and small CatD-positive vesicles were observed [14].
• The cDNA encoding human stratum corneum chymotryptic enzyme (SCCE); an epidermal serine-proteinase which was recently purified from human stratum corneum, was isolated from a keratinocyte derived library [8].
• Compared with healthy and benign ovarian tissues and nonovarian tumors that metastasized to the ovary, malignant ovarian tumor cytosols highly overproduced hK7 (P <0.001) [15].

Associations of KLK7 with chemical compounds

• In contrast to involucrin, which was expressed by all suprabasal keratinocytes, SCCE was expressed only by high suprabasal cells [16].
• In order to investigate the mechanism of glycolic acid (GA) function in human stratum corneum, we monitored changes in cathepsin D-like (CD) and chymotrypsin-like (SCCE) proteinases for 3 weeks following topical GA application (50% w/v, pH 0.9) for 30 min to human skin [17].
• Expression of stratum corneum chymotryptic enzyme in reconstructed human epidermis and its suppression by retinoic acid [18].
• We found expression of SCCE in luminal parts of the pilary canal, common sebaceous ducts and proximal sebaceous ducts [19].

Enzymatic interactions of KLK7

• Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum chymotryptic enzyme in vitro [20].

Regulatory relationships of KLK7

• Moreover, our results suggest that SCTE is able to activate the proform of SCCE [21].
• LEKTI was expressed earlier than KLK7 and KLK5 [13].

Other interactions of KLK7

• Using the recombinant form of CDSN, either with its N-glycan chain or enzymatically deglycosylated, we also demonstrated that oligosaccharide residues do not protect CDSN against proteolysis by SCCE [21].
• This was in spite of very low levels of KLK14 protein compared to KLK5 and KLK7 [22].
• In this study, we examined the level of mRNA expression of the KLK7 and KLK8 genes in 73 intracranial tumors using qualitative RT-PCR [11].
• Quantitative reverse transcription-PCR assay for detection of mRNA encoding full-length human tissue kallikrein 7: prognostic relevance of KLK7 mRNA expression in breast cancer [3].
• OBJECTIVE: To determine whether the Stratum Corneum Chymotryptic Enzyme (SCCE), a novel serine protease known to contribute to the cell shedding process by catalyzing the degradation of intercellular cohesive structures at the skin surface, is overexpressed in human cervical tumors [23].

Analytical, diagnostic and therapeutic context of KLK7

• RESULTS: We here report that patients with KLK7-negative tumors have a significantly higher disease-free survival than patients with KLK7-positive tumors [2].
• Immunohistochemistry with the antibodies reacting with pro-stratum corneum tryptic enzyme showed a staining pattern similar to stratum corneum chymotryptic enzyme-specific antibodies, i.e., the expression was confined to cornifying epithelia with a need of desquamation-like processes [24].
• The aim of this study was to determine whether hK7, measured quantitatively by ELISA in ovarian cancer cytosols, is a prognostic biomarker for ovarian cancer [15].
• We screened the SCCE gene for variations and performed a case-control study on 103 atopic dermatitis patients and 261 matched controls [25].
• CONCLUSIONS: The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer [26].

References