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Role of Wnt canonical pathway in hematological malignancies

DOI: 10.1186/1756-8722-3-33

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Abstract:

Wnt canonical signaling pathway acts a significant part in embryonic development and in maintenance of organs and tissues in adults. In the past two decades, medical scientists have devoted themselves to understanding the cellular and molecular mechanisms of Wnt signaling. A lot of studies indicate that Wnt canonical pathway involves in the pathogenesis of a range of disease including many kinds of carcinomas. Hematological malignancies are the types of carcinoma that affect blood, bone marrow and lymph nodes. They may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The incidence of hematological malignancies has been increasing steadily in the world for the past years, but their etiology and pathogenesis has not been well understood involving areas of chromosome aberrations, apoptosis inhibition, abnormal activation of signaling pathways, angiogenesis, et al. In this review, we focus on the role of Wnt canonical signaling in carcinomas, especially in hematological malignancies, and then disclose potential therapeutic opportunities of this pathway in hematological malignancies.Wnt signaling pathways are categorized as "canonical "and "non-canonical" Wnt pathways, which are β-catenin-dependent and β-catenin-independent signaling pathways, respectively. Here we will emphatically point out the role of Wnt canonical pathway in hematological malignancies. A simplified model of Wnt canonical pathway is delineated in Fig. 1. Wnts is a group of secreted cysteine-rich glycoproteins, which includes at least 19 identified members in diverse species ranging from round worm and insects to human[1]. In the absence of a Wnt ligand binding to its receptor complex, the cytoplasmic β-catenin is degraded by the "destruction complex". In this complex, Axin acts as an scaffold protein, which adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK-3β) and casein kinase 1α (CK1α) bind to facilitate the sequential phophorylation of β-cat

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