scholarly journals The role of the Wnt signaling pathway in cancer stem cells: prospects for drug development

2014 ◽  
pp. 1 ◽  
Author(s):  
Michael Kahn ◽  
Yong-mi Kim
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Drug Development ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

scholarly journals Wnt-signaling pathway in pathogenesis of glioblastoma multiforme

2019 ◽  
Vol 5 (4) ◽  
pp. 94-103
Author(s):  
Yu. D. Vasilets ◽  
N. E. Arnotskaya ◽  
I. A. Kudryavtsev ◽  
V. E. Shevchenko
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Biological Processes ◽  
Current Standard ◽  
Immune Resistance ◽  
Oncogenic Driver ◽  
And Migration

The Wnt-signaling pathway regulates various biological processes, such as embryonic development, self-renewal, proliferation, differentiation and migration of stem cells. The Wnt-signaling is involved in tumor progression by aberrant activation in stem-like cells, called cancer stem cells, in different kinds of tumor, including multiform glioblastoma. The Wnt-signaling promotes stemness, invasion, metastasis, therapeutic and immune resistance of cancer stem cells in multiform glioblastoma. To summarize, targeting the Wnt-signaling pathway as an oncogenic driver is the future hope for effective therapy of glioblastoma for which current standard therapy is not effective.In this review, we focused on functions of the Wnt-signaling in cancer stem cells and involvement of the Wnt-signaling pathway in gliomagenesis.

Polycomb Repressive Complex 1 Enhances HSC Self-Renewal through Repressing the Canonical Wnt Signaling Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2378-2378
Author(s):  
Sisi Chen ◽  
Xicheng Liu ◽  
Rui Gao ◽  
Michihiro Kobayashi ◽  
Hao Yu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Canonical Wnt Signaling ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Canonical Wnt

Abstract Polycomb group (PcG) proteins are epigenetic gene silencers that have been implicated in stem cell maintenance and cancer development. Genetic and biochemical studies indicate that Polycomb group proteins exist in at least two protein complexes, Polycomb repressive complex 2 (PRC2) and Polycomb repressive complex 1 (PRC1), that act in concert to initiate and maintain stable gene repression. While studies on individual PRC1 component suggest that PRC1 plays an important role in hematopoiesis, how PRC1 regulates transcriptional repression in hematopoietic stem cells (HSCs) is largely unknown. Bmi1 and Mel18 are two major homologs of the PCGF subunit within the PRC1 complex. Bmi1 is a positive regulator of HSC self-renewal; however, the role of Mel18 in hematopoiesis has been controversial. To determine whether Bmi1 and Mel18 play redundant or distinct role in HSC self-renewal, we have generated Bmi1 and Mel18 conditional knockout mice. While acute deletion of Mel18 affects neither HSC frequency nor lineage commitment, we found that Mel18-deficent hematopoietic progenitor cells showed enhanced replating potential compared to wild type cells. To determine the role of Mel18 in HSC self-renewal, we performed serial HSC transplantation assays and found that the repopulating ability of Mel18-/- HSCs was significantly higher than WT HSCs in both primary and secondary transplantation assays, demonstrating that the loss of Mel18 enhances HSC self-renewal in vivo. We hypothesize that loss of Bmi1 and Mel18 in hematopoietic stem cells will disrupt PRC1 complex and impairs HSC self-renewal. To determine the role of PRC1 complex in HSCs, we analyzed the HSC behavior in Bmi1 and Mel18 double-deficient mice. While we found that Bmi1-deficient HSCs showed decreased repopulating potential compared to WT HSCs 16 weeks following transplantation, loss of both Bmi1 and Mel18 in HSCs resulted in even more severe self-renewal defects. In addition, loss of both Bmi1 and Mel18 resulted in decreased myeloid differentiation and increased B cell differentiation compared to WT, Mel18 KO, and Bmi1 KO mice. These data demonstrate that Bmi1 and Mel18 have non-overlapping role in HSC maintenance and lineage commitment. Given that Bmi1 plays a dominant role in the PRC1 complex, we decided to identify Bmi1 target genes in hematopoietic stem cells to understand how PRC1 complex regulates HSC self-renewal. We performed transcript profiling assays to compare gene expression in HSCs isolated from wild type and Bmi1-/- mice. The Ingenuity Pathways indicates that the canonical Wnt signaling is significantly elevated in Bmi1 null HSCs compared to WT HSCs. We confirmed the upregulation of several genes of the Wnt pathway in Bmi1 null HSCs by quantitative real-time PCR analysis. To determine whether Bmi1 can repress the activation of Wnt signaling in cells, we utilized the Top-Flash Wnt reporter system. Stimulation of 293T cells with Wnt3a activates the Wnt reporter and this activation can be efficiently repressed by Bmi1. Furthermore, we detected the association of Bmi1 with the Lef1, Tcf4, and Axin2 promoters in Baf3 cells by ChIP experiment. Thus, Bmi1 directly represses the expression of several Wnt genes in hematopoietic cells. To determine the functional significance of activation of Wnt signaling in Bmi1 null HSCs, we have generated R26StopFL Bmi1-Apcf/f-Mx1-Cre+ and Bmi1f/f-Ctnnb1f/f-Mx1-Cre+ mice. Loss of Apc in hematopoietic cells activates the Wnt signaling pathway and impairs HSC self-renewal. We found that expressing three-copies of Bmi1 from the Rosa26 locus enhanced the self-renewal capabilities of Apc deficient HSCs in transplantation assays. Ctnnb1 encodes b-catenin and loss of Ctnnb1 in HSCs diminishes Wnt signaling. Acute deletion of Bmi1 in hematopoietic compartments resulted in decreased bone marrow cellularity and enhanced apoptosis of hematopoietic stem and progenitor cells. Deletion of Ctnnb1 in Bmi1 null hematopoietic cells rescued these defects. Thus, impaired HSC self-renewal seen in Bmi1 null mice is, at least in part, due to activation of the canonical Wnt signaling pathway. Taken together, we demonstrate that PRC1 complex enhances HSC self-renewal through inhibiting the canonical Wnt signaling. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proteins of the Wnt signaling pathway as targets for the regulation of CD133+ cancer stem cells in glioblastoma

2019 ◽  
Author(s):  
Valery Shevchenko ◽  
Nataliya Arnotskaya ◽  
Maria Korneyko ◽  
Sergry Zaytsev ◽  
Yuriy Khotimchenko ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

scholarly journals Wnt-signaling pathway in the cancer stem cells of glioblastoma

2018 ◽  
Vol 29 ◽  
pp. vi26-vi27
Author(s):  
I.S. Bryukhovetskiy ◽  
V. Shevchenko ◽  
Y. Khotimchenko
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway

PlGF knockdown induced apoptosis through Wnt signaling pathway in gastric cancer stem cells

2018 ◽  
Vol 120 (3) ◽  
pp. 3268-3276 ◽  
Author(s):  
Hassan Akrami ◽  
Kiumars Mehdizadeh ◽  
Behrouz Moradi ◽  
Diba Borzabadi Farahani ◽  
Kamran Mansouri ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Gastric Cancer Stem Cells ◽  
Induced Apoptosis
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