Abstract: BACKGROUND: ADP-ribosylation factor (ARF)-like 4c (Arl4c) has been reported to promote tumorigenesis in colorectal and lung cancers and may represent a novel therapeutic target. The aim of this study was to investigate the expression of ADP-ribosylation factor (ARF)-like 4c (Arl4c) in colorectal cancer (CRC) in Chinese populations and an AOM/DSS-induced mouse colorectal carcinogenesis model, and its prognostic value in patients with CRC. MATERIALS AND METHODS: Expression of Arl4c in CRC patients and AOM/DSS-induced colorectal tumors was detected using immunohistochemistry and real- Real time PCR. In addition, the correlations between Arl4c expression and clinicopathological characteristics and overall survival were evaluated using…Kaplan-Meier analysis. RESULTS: The Arl4c was statistically significantly overexpressed in CRC tissues relative to adjacent normal tissue (p= 0.001). CRC patients with high Arl4c expression tended to show poorer survival than patients with lower Arl4c expression (p= 0.069). However, the level of Arl4c expression was not visibly correlated with age, gender or tumor stage. In addition, increased expression of Arl4c was also found in AOM/DSS-induced colorectal tumors (p= 0.001), which indicated that Arl4c might play an important role in colon tumorigenesis. CONCLUSIONS: Results indicated that overexpression of Arl4c might contribute to the tumorigenesis and might play a pivotal role in the progression of CRC.
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Abstract: The accumulation of amyloid-β (Aβ) peptides in senile plaques is one of the hallmarks of Alzheimer's disease (AD) progression. The endocytic pathway has been proposed as a major subcellular site for Aβ generation while the compartments in which Aβ-degrading proteases interact with Aβ are still elusive. It was suggested that extracellular Aβ degradation may take place by plasma-membrane associated proteases or by extracellular proteases, among which insulin-degrading enzyme (IDE) is the most relevant. However, the mechanisms of IDE secretion are poorly understood. In the present study we used N2a cells to explore if IDE is indeed released through exosomes and…the effect of exosomes release on extracellular levels of Aβ. We demonstrated that proteolytically-active plasma membrane associated-IDE is routed in living N2a cells to multivesicular bodies and subsequently, a major fraction is sorted to exosomes. We described that extracellular IDE levels decrease if the generation of multivesicular bodies is interfered and may be positively modulated by exosomes release under stress-induced conditions. Our results reinforce the relevance of functional IDE in the catabolism of extracellular Aβ.
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