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Background: Increased protein N-glycosylation and aberrant Wnt signaling are features of oral cancer. Results: Overexpression of pro-migratory protein CTHRC1 is due to hyperglycosylation and transcriptional activation by canonical Wnt. Conclusion: N-Glycosylation collaborates with canonical Wnt to induce CTHRC1 and drive OSCC cell migration. Significance: Elucidating how N-glycosylation impacts tumor-promoting proteins is critical to understand cancer development and progression.

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Oral cancer is one of the most aggressive epithelial malignancies, whose incidence is on the rise. Previous studies have shown that in a subset of human oral squamous cell carcinoma (OSCC) tumor specimens, overexpression of the DPAGT1 gene, encoding the dolichol-P-dependent N-acetylglucoseamine-1-phosphate transferase, a key regulator of the metabolic pathway of protein N-glycosylation, drives tumor cell discohesion by inhibiting E-cadherin adhesive function. Recently, we reported that DPAGT1 was a target of the canonical Wnt signaling pathway. Here, we link overexpression of DPAGT1 in human OSCC tumor specimens to aberrant activation of canonical Wnt signaling. We report dramatic increases in β- and γ-catenins at the DPAGT1 promoter and correlate them with reduced expression of a Wnt inhibitor, Dickkopf-1 (Dkk-1). Using human squamous carcinoma cell lines of the head and neck, we show that partial inhibition of DPAGT1 reduces canonical Wnt signaling, indicating that DPAGT1 and canonical Wnt signaling function in a positive feedback loop. We provide evidence that E-cadherin inhibits DPAGT1, canonical Wnt signaling and the OSCC cancer phenotype by depleting nuclear β-and γ-catenins, with hypoglycosylated E-cadherin being the most effective.This suggests that in human OSCC, extensive N-glycosylation of E-cadherin compromises its ability to inhibit canonical Wnt signaling and DPAGT1 expression. Our studies reveal a novel interplay between DPAGT1/N-glycosylation and canonical Wnt signaling and suggest that dysregulation of this crosstalk is a key mechanism underlying OSCC. They also suggest that partial inhibition of DPAGT1 may represent an effective way to restore normal interactions among these essential pathways in oral cancer.

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PurposeThis meta-analysis aimed to review the published outcomes of parotid non-Hodgkin lymphoma (NHL) pertaining to different treatment modalities.Materials and MethodsA total of 48 journal articles published between 1993 and 2015, comprising 742 cases of parotid NHL, were initially evaluated. In total, 108 patients from 12 studies who had sufficient data for analysis, including age, tumor histopathology, treatment modality, and outcome at final follow-up, were included. Patients were randomly assigned to different categories on the basis of histopathology and treatment modality. Groups were compared using Kaplan-Meier survival curve analysis and the Mann-Whitney U test.ResultsLog-rank tests demonstrated that for early-stage (I and II) parotid NHL of all histopathology variants, radiation therapy significantly improved the survival rate versus chemotherapy (P = .043), as well as combined treatment with chemotherapy and radiation therapy (P = .023). For early-stage diffuse large B-cell lymphoma, combined treatment significantly improved survival versus single treatment (P = .028). No treatment was received by seven patients with early-stage mucosa-associated lymphoid tissue lymphoma after undergoing parotidectomy. When the clinical outcomes of these patients were compared with those of other patients with the same histology who underwent further treatment, no significant differences were noted in survival outcomes.ConclusionRadiation therapy seems to be a valid treatment of early-stage parotid NHL. However, for diffuse large B-cell lymphoma, survival was higher with combined treatment versus single treatment. For early-stage parotid mucosa-associated lymphoid tissue lymphoma, complete excision of the tumor through superficial parotidectomy may have similar survival outcome.