Aberrant expression of β-catenin and its association with ΔNp63, Notch-1, and clinicopathological factors in oral squamous cell carcinoma

Abstract

The present study focuses on the correlation between the expression pattern of β-catenin (component of Wnt signaling), ΔNp63 (proliferation marker), and Notch 1 (transmembrane receptor) in oral squamous cell carcinoma. The study also aims to investigate the interaction between β-catenin and ΔNp63 in oral cancer. Furthermore, we also analyzed the prognostic significance of β-catenin, ΔNp63, and Notch 1 in oral squamous cell carcinoma. Immunohistochemical analysis of β-catenin, ΔNp63, and Notch 1 were done in 62 cases of oral squamous cell carcinoma. Co-immunoprecipitation analysis was done to study the possible interaction between β-catenin and ΔNp63 in oral cancer. Kaplan-Meier method was used to estimate overall and disease-free survival, and the Log-rank test was used to compare the resulting curves. Statistically significant positive correlation was found between the localization of β-catenin and the expression of ΔNp63 (p = 0.001**, r (s) = 0.427), whereas, no significant association was found between the expression pattern of β-catenin and Notch 1. Interestingly, interaction between β-catenin and ΔNp63 was observed in oral carcinoma. Moreover, β-catenin and ΔNp63 may be related to worst survival in oral carcinoma. Statistically significant positive association between localization of β-catenin and expression of ΔNp63 suggests that they might have dependent roles in maintaining the proliferation of oral carcinoma cells. In addition, the downregulated expression of Notch 1 was related to invasion and differentiation status of oral carcinoma cells. Furthermore, β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma. On the other hand, interaction of β-catenin with ΔNp63 may be a key event in maintaining the proliferation of oral carcinoma cells. The present study indicates that β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma and the interaction of β-catenin with ΔNp63 may be a crucial event in regulating proliferation and differentiation of oral carcinoma cells, which may be used as a target for therapeutic implications.

Association of differential β‐catenin expression with Oct‐4 and Nanog in oral squamous cell carcinoma and their correlation with clinicopathological factors and prognosis

“…This suggests that the β-catenin pathway might be re-activated and involved in oral carcinogenesis. Consistent with our previous findings [5], the expression of β-catenin was significantly correlated with lymph node metastasis, stage and grade of oral squamous cell carcinoma. This indicates that the expression of β-catenin may be related to the invasion and differentiation status in oral carcinoma cells.…”

“…The signals were detected using Amersham ECL plus kit according to the manufacturer's protocol. For coimmunoprecipitation, the β-catenin immune complex was prepared as described in our previous report [5] Immunoblot analysis was performed as described above. The cell lysates were immunoprecipitated with IgG (Santa Cruz Biotech, USA) and used as negative control.…”

“…Previously, we have found a positive relationship and interaction between β-catenin and keratinocyte stem/progenitor cell marker ∆Np63 in maintaining proliferation of oral carcinoma cells [5]. Therefore, to extend our knowledge on the relationship between β-catenin and other stem cell markers, we have investigated the correlation between Oct-4, Nanog and β-catenin in oral carcinoma.…”

“…In addition to its role in maintaining stemness of embryonic stem cells, β-catenin was found to have a significant role in several tumors including oral squamous cell carcinoma, particularly the malignant transformation of oral dysplasia is associated with the intracellular expression of β-catenin. [5,9]. The expression of β-catenin was associated with invasion and metastasis of oral carcinoma cells thereby leading to poor prognosis [5].…”

“…[5,9]. The expression of β-catenin was associated with invasion and metastasis of oral carcinoma cells thereby leading to poor prognosis [5]. Recently, it was found that β-catenin maintains the self-renewal of embryonic stem cells by interacting with Oct-4 and subsequently upregulating Nanog [7].…”