Aldehyde dehydrogenase 1 (ALDH1) is a cancer stem-like cell (CSC) marker in human cancers; however, the specific ALDH1-regulated function and its underlying signalling pathways have not been fully demonstrated. Here, we investigated the ALDH1-regulated function and its underlying signalling and tested whether all-trans retinoic acid (ATRA) can suppress ALDH1-regulated tumour behaviour in ovarian cancer cells. By modulating ALDH1 expression using flow cytometry enrichment and exogenous overexpression or knockdown, we showed that the ALDH1 activity is positively correlated with stemness in ovarian cancer cells according to measures such as sphere formation and CSC marker expression as well as tumourigenesis in a mouse xenograft model. The findings indicate that the ALDH1 directly regulates the functions of ovarian cancer cells. We also showed that ALDH1 can regulate the expression of FoxM1 and Notch 1, which are involved in the downstream signalling of ALDH1-mediated biofunctions. Inhibition of FoxM1 by Thiostrepton and of Notch1 by DAPT downregulated the sphere formation ability of cells. ATRA reduced ALDH1 expression, suppressed tumour formation and inhibited sphere formation, cell migration and invasion in ALDH1-abundant ovarian cancer cells. We conclude that ATRA downregulates ALDH1/FoxM1/Notch1 signalling and suppresses tumour formation in ovarian cancer cells.
Glycosylation plays a role in regulating many biological activities, including protein folding and cell surface expression of biomolecules. However, the importance of glycosylation for KCC4 function has not previously been demonstrated. Site-directed mutagenesis was performed on the four putative extracellular N-linked glycosylation sites of KCC4 to determine the role of these sites in KCC4 half-life, cell surface expression, and transporter activity, as well as in KCC4-dependent tumor formation. We showed that triple (N312/331/344/Q) and quadruple (N312/331/344/360/Q) mutations of N-linked glycosylation sites disrupt the N-linked glycosylation of KCC4, resulting in the accumulation of KCC4, predominantly in the endoplasmic reticulum (ER) and not at the cell surface. Further investigation indicated that mutations of the central two (N331/344/Q) N-linked glycosylation sites inhibit the membrane trafficking of KCC4. Our data suggest that the glycan moieties at the N331 and N344 sites were Endo H-resistant, complex-form structures, and that the N312 and N360 sites were Endo H-sensitive, high mannose-containing structures. Under hypotonic stress conditions, the ability to adapt to changes in intracellular chloride ion concentrations and RVD (regulatory volume decrease) activities were less efficient in cells containing the deglycosylated form of KCC4 that were not expressed at the cell surface. Deglycosylated forms of KCC4 also demonstrated decreased tumor formation and lung colonization in mouse xenografts. The difference in glycan complexity may account for the differential impact of each branch on the biological effects of KCC4. We propose that glycosylation is essential for the surface expression, stabilization, and bioactivity of KCC4.
Background Hernia repair with mesh in patients with incarcerated or strangulated hernias is controversial. Moreover, the use of mesh for hernia repair with concomitant bowel resection poses a great dilemma. This study compared the outcomes of mesh and anatomic repairs in patients with acutely incarcerated or strangulated hernias. Methods PubMed, Embase, and Cochrane databases were searched for studies published before November 2019. Randomized controlled trials (RCTs) and prospective studies were included. We conducted meta-analyses using a random-effects model. The treatment outcome was measured by the incidence of surgical site infection (SSI), seroma formation, and hernia recurrence postoperatively. Results Two RCTs and six prospective studies with 978 patients were included. No significant difference in SSI incidence was observed between patients with incarcerated hernia from the mesh and anatomic repair groups. Recurrence was significantly lower in mesh repair group than in anatomic repair group (odds ratio, 0.08; 95% confidence interval, 0.01-0.45). Only two patients needed to have mesh explantation due to mesh infection. In the setting of hernia repair with concomitant bowel resection, the SSI rate with mesh repair was slightly higher, but most cases of infections were well controlled with conservative antibiotic therapy. Conclusions Mesh repair for incarcerated or strangulated hernias was feasible with a great benefit of lower recurrence rates. However, due to limited data, drawing conclusions regarding the use of mesh for hernia repair with concomitant bowel resection was difficult. Further studies with preset criteria for evaluating patients undergoing concomitant bowel resection may help elucidate this issue.Yu-Te Lin and Tzu-Yu Weng contributed equally to this study.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.