The Wnt signaling pathway in cancer

Abstract

The Wnt signaling pathway is critically involved in both the development and homeostasis of tissues via regulation of their endogenous stem cells. Aberrant Wnt signaling has been described as a key player in the initiation of and/or maintenance and development of many cancers, via affecting the behavior of Cancer Stem Cells (CSCs). CSCs are considered by most to be responsible for establishment of the tumor and also for disease relapse, as they possess inherent drug-resistance properties. The development of new therapeutic compounds targeting the Wnt signaling pathway promises new hope to eliminate CSCs and achieve cancer eradication. However, a major challenge resides in developing a strategy efficient enough to target the dysregulated Wnt pathway in CSCs, while being safe enough to not damage the normal somatic stem cell population required for tissue homeostasis and repair. Here we review recent therapeutic approaches to target the Wnt pathway and their clinical applications.

Overexpression of MYC binding protein promotes invasion and migration in gastric cancer

“…The TCF/LEF axis serves a crucial role in the Wnt/β-catenin signaling pathway (18). A previous study observed that the transcription of a series of target genes within the Wnt/β-catenin signaling pathway was activated following the formation of a TCF/LEF/β-catenin complex in the nucleus, which regulated cellular biological activities and promoted the migratory and invasive abilities of tumor cells (19). Recent studies have also indicated that MYCBP is associated with tumorigenesis in a variety of tumor types, including colon cancer and glioma (20,21).…”

Wnt3a expression is associated with poor prognosis of esophageal squamous cell carcinoma

“…The Wnt signaling pathway is pivotal in embryogenesis and development and aberrant activation of canonical Wnt signaling is also widely implicated in a number of human disease such as cancer (2,3). β-catenin, which is a central molecule in the canonical Wnt pathway, translocates from a free cytosolic form to the nucleus and then plays a role as a cofactor with T-cell factor/lymphoid enhancer factor in order to trigger gene transcription (4)(5)(6).…”

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

“…Silencing of these genes via hypermethylation of their promoters has been shown to be part of the pathogenesis in a plethora of human malignancies. [1][2][3][4][5][6] Aberrant regulation of the Wnt signaling pathway is known to play a role in tumorigenesis and maintenance of cancer stem cells. 3,4,28 The Wnt pathway can be activated aberrantly not only by mutations of genes functioning in Wnt signaling such as APC and CTNNB1 but also by dysregulation of secreted antagonists.…”

“…9 Deregulated activation of the canonical Wnt pathway is also observed in leukemia. 1,[10][11][12][13] The hematopoietic system of the adult organism is composed of cells with a short life span, which are renewed by differentiating from a small population of hematopoietic stem cells (HSCs). Nuclear β-catenin is a key molecule that drives self-renewal.…”

“…[1][2][3][4][5][6] Wnt/β-catenin signaling has pivotal roles both in early developmental stages and in tissue maintenance of adults. The pathway operates by regulating specific genes that function in cell fate, proliferation, polarity, migration, and differentiation.…”