KLK6 (Kallikrein Related Peptidase 6)

Screening for protease inhibitors that would rescue stress-induced decreases in MMP-2 activity identified a single serine protease inhibitor: aprotinin...In conclusion, we identify a novel stress-induced extracellular network that regulates MMP-2 activity and cell motility. We identified KLK6 as a stress-induced extracellular protease leading to decreased MMP-2 activity and cellular invasion, while eHSP90α is required for the rescue of MMP-2 activity once KLK6 is neutralized.

Screening for protease inhibitors that would rescue stress-induced decreases in MMP-2 activity identified a single serine protease inhibitor: aprotinin...We identify a novel stress-induced extracellular network that regulates MMP-2 activity and cell motility. We identified KLK6 as a stress-induced extracellular protease leading to decreased MMP-2 activity and cellular invasion, while eHSP90α is required for the rescue of MMP-2 activity once KLK6 is neutralized.

Meanwhile, we identified KLK6 as a potential promoter of tumor progression and immunosuppression. Targeting the succinylation pathway, particularly KLK6, may represent a promising therapeutic strategy for LUAD.

This validated mitochondrial risk model delivers a clinically actionable biomarker for BLCA prognosis stratification and guides personalized therapeutic selection, enabling precision treatment intensification.

RCC harbors an immunosuppressive niche driven by T-cell exhaustion, mast cell reprogramming, and expansion of a malignant CASC15⁺KLK6⁺ epithelial subpopulation. Targeting MIF and CD99 signaling networks represents a potential therapeutic strategy for right-sided colon cancer.

Our results provide an explanation for the presence of alternatively spliced APP isoforms in the brains of patients with Alzheimer's disease (AD) and reveal the roles of APPI in APP cleavage and in the formation, aggregation and toxicity of both extra- and intracellular Aβ peptide fragments. Our results suggest that APPI may serve as a dual inhibitor, disrupting both KLK6 proteolytic activity and Aβ42 aggregation, thereby offering a potential therapeutic agent for reducing amyloid beta toxicity in AD.

Klk8 expression was higher in microglia than in oligodendrocytes, and Klk6 expression was higher in astrocytes than in oligodendrocytes. The expression levels of Klk6 and Klk8 in microglia and astrocytes were uncorrelated with the expression of myelin-related genes in oligodendrocytes, suggesting that these genes in microglia and astrocytes may have functional roles other than myelination.

KLK6 also impacted genes associated with immune checkpoint inhibition and decreased cell responses to anti-PD-1 checkpoint blockade in vitro. Our study identified KLK6 as a drug target as it regulates neutrophil recruitment, immunosuppression, and cell responses to anti-PD-1 therapy in a biomaterial-based disease model.

Overexpression of PRDX2 in human neuroblastoma cells correlated with enhanced antiviral gene expression, p-STAT1, p-AKT (ser473), and viral replication. Thus, our comprehensive proteomic analysis of CSF identifies PRDX2 as an important circulatory protein, differentially expressed between JEV and ST, with high specificity and enhancing viral propagation, underscoring its role in viral propagation and pathogenesis.

In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT.

This study elucidates significant alteration in the cellular ecosystems and intercellular signaling within the tumor immune microenvironment across the NAT-HGIN-GBC sequence. It identifies TOP2A, TWEAK, and FN14 as potential biomarkers and therapeutic targets for GBC.

Notably, among these calcitriol-regulated microRNAs are some involved in cervical cancer biology, such as miR-6129, miR-382, miR-655, miR-211, miR-590, miR-130a, miR-301a, and miR-1252. Collectively, these findings suggest that calcitriol exhibits a significant antitumor effect in this advanced cervical cancer model by blocking critical processes for tumor progression, underscoring the importance of maintaining adequate vitamin D nutritional status.