Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis.

Kallikrein-related peptidases (KLKs) are implicated in many cancer-related processes. KLK6, one of the 15 KLK family members, is a promising biomarker for diagnosis of many cancers and has been associated with poor prognosis of colorectal cancer (CRC) patients. Herein, we evaluated the expression and cellular functions of KLK6 in colon cancer-derived cell lines and in clinical samples from CRC patients. We showed that, although many KLKs transcripts are upregulated in colon cancer-derived cell lines, KLK6, KLK10, and KLK11 are the most highly secreted proteins. KLK6 induced calcium flux in HT29 cells by activation and internalization of protease-activated receptor 2 (PAR2). Furthermore, KLK6 induced extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation. KLK6 suppression in HCT-116 colon cancer cells decreased the colony formation, increased cell adhesion to extracellular matrix proteins, and reduced spheroid formation and compaction. Immunohistochemistry (IHC) analysis demonstrated ectopic expression of KLK6 in human colon adenocarcinomas but not in normal epithelia. Importantly, high levels of KLK6 protein were detected in the ascites of CRC patients with peritoneal metastasis, but not in benign ascites. These data indicate that KLK6 overexpression is associated with aggressive CRC, and may be applied to differentiate between benign and malignant ascites.

Increased spindle density correlates with sleep continuity improvements following an eight-week course of a melatonin agonist in people with depression: A proof-of-concept study with agomelatine.

Sleep fragmentation and reductions in sleep spindles have been observed in individuals with depression. Sleep spindles are known to play a protective role for sleep, and there are indications that melatonin agents can enhance spindles in healthy people. Whether agomelatine, a melatonin agonist indicated for the treatment of depression, may increase spindle density sufficiently to impact sleep continuity in people with depression remains unknown. This proof-of-concept study investigated changes in spindles following agomelatine intake in young adults with depression and assessed how they may relate to potential changes in sleep continuity and depressive symptoms. This study was based on an open-label design. Fifteen participants between 17 and 28 years of age (mean = 22.2; standard deviation [SD] = 3.4) with a diagnosis of a depressive disorder underwent polysomnography before and after an intervention including a 1 hr psychoeducation session centered on sleep and circadian rhythms, and an 8-week course of agomelatine (25-50 mg) with a guided sleep phase advance. Fast spindle density significantly increased from pre- to post-intervention. This increase in spindle density significantly correlated with a reduction in wake after sleep onset, and a similar trend was found with increased sleep efficiency. There was no significant correlation between spindle parameters and depressive symptoms. These findings suggest that agomelatine may contribute to enhanced sleep consolidation, possibly in part through the modulation of spindle production. This should be confirmed by larger randomized control trials.