Wnt/Wingless signaling pathway is involved in various pathological conditions including cancer. Wnt proteins' binding with their transmembrane receptors activate a canonical pathway, which is characterized by accumulation of p-catenin in the cytoplasm and in the nucleus. Activation of the receptors leads to the phosphorylation of the disheveled protein, through its association with AXIN1 and then prevents glycogen synthase kinase 3 from phosphorylating critical substrates, such as p-catenin. Thus, inhibiting its cytoplasm degradation. Excess p-catenin then goes to the nucleus to form an active transcriptional complex with T-cell factor, which activates transcription of target genes including c-myc and cyclin D1. Although, different components of the Wnt-signaling pathway are mutated in human cancer, only a few studies reported mutation of p-catenin and axin 1 in cervical cancer (23,24). However, a recent study (25) suggests that transformation of HPV-expressing human keratinocytes requires activation of the Wnt pathway as the second hit and that such activation may serve as a screening tool in HPV-positive population to detect cervical malignant progression.
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