Wnt signaling in cancer stem cells and colon cancer metastasis

Basu, Sayon; Haase, Gal; Ben-Ze’ev, Avri

doi:10.12688/f1000research.7579.1

Cited by 159 publications

(148 citation statements)

References 90 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…The critical feature of CSCs is self-renewal, which is responsible for cancer drug resistance, metastasis, and recurrence [19, 20, 45]. We found that Lgr5-positive subpopulations generated significantly more multipotent spheres than did Lgr5-negative subpopulations, indicating a remarkable self-renewal advantage of Lgr5-positive cells.…”

Section: Discussionmentioning

confidence: 87%

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Leng

Xia

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Although EpCAM+CD44+ cells exhibit more stem-like properties than did EpCAM-CD44- cells, the specificity of EpCAM combined with CD44 in defining CSCs needs further improvement. Lgr5 is used as a biomarker to isolate cancer stem cells (CSCs) in colorectal cancer. However, it remains unclear whether Lgr5, along with EpCAM and CD44, can further identify and define CSCs in colorectal cancer. Methods: Lgr5+CD44+EpCAM+, Lgr5+CD44+EpCAM-, Lgr5+CD44-EpCAM+, Lgr5-CD44+EpCAM+, and Lgr5-CD44-EpCAM-cells were separately isolated using fluorescence-activated cell sorting (FACS). Colony formation, self-renewal, differentiation, and tumorigenic properties of these cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression of stemness genes and CSC- and epithelial-mesenchymal transition (EMT)-related genes, such as KLF4, Oct4, Sox2, Nanog, CD133, CD44, CD166, ALDH1, Lgr5, E-cadherin, ZO-1, Vimentin, Snail, Slug, and Twist, was examined using real-time PCR. Results: Lgr5-positive subpopulations exhibited higher capacities for colony formation, self-renewal, differentiation, and tumorigenicity as well as higher expression of stemness genes and mesenchymal genes and lower expression of epithelial genes than did Lgr5-negative subpopulations. Conclusion: Our data revealed that tumorigenic cells were highly restricted to Lgr5-positive subpopulations. Most importantly, Lgr5+CD44+EpCAM+ cells exhibited more pronounced CSC-like traits than did any other subpopulation, indicating that Lgr5 combined with CD44 and EpCAM can further improve the stem-like traits of CSCs in colorectal cancer.

show abstract

Section: Discussionmentioning

confidence: 87%

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Leng

Xia

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…The canonical Wnt pathway is an evolutionarily conserved mechanism of stem cell regulation [24, 25]. Aberrant regulation of the Wnt pathway causes malignant proliferation, and its activation helps maintain the CSC reservoir that contributes to CRC stemness, recurrence, and chemoresistance [26, 27].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Peptidase 22 Contributes to Colorectal Cancer Stemness and Chemoresistance via Wnt/β-Catenin Pathway

Jiang

Song

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Two major barriers to the successful treatment of colorectal cancer (CRC) are the development of stem cell-like characteristics (stemness) and chemoresistance. Ubiquitin-specific peptidase 22 (USP22) is a deubiquitinating enzyme and putative CRC marker that has emerged as a potential cause of both phenomena in CRC. There is evidence that USP22 acts through the Wnt/β-catenin pathway and that downregulation of the latter may reduce chemoresistance. Methods: In this study, we used CRC tissue specimens from human patients as well as human CRC cell lines to evaluate the role of USP22 in CRC stemness and chemoresistance in vitro and in vivo. RT-PCR and western blot were used for gene expression analyses. Immunohistochemistry was performed for USP22 expression in clinical samples. CD133 levels were analyzed by flow cytometry. Sphere formation and MTT assays were used for self-renewal and proliferation analysis. Chemoresistance was evaluated by cell viability and sphere formation assays. Results: We found a significant increase of USP22 in recurrent CRC and chemoresistant CRC cells as compared to primary CRC and non-chemoresistant CRC cells, respectively. We then demonstrated that USP22 mediates CRC cell chemoresistance through the Wnt/β-catenin pathway and that reducing USP22 in CRC cells diminishes chemoresistance. Conclusions: Having established the crucial role of USP22 in CRC stemness and chemoresistance, this study suggests that USP22 may be an ideal genetic target in the treatment of chemoresistant CRC.

show abstract

“…[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. For example, diminished expression caused by promoter methylation of Wnt antagonists genes sFRP1 and WIF1 results in unregulated increase of ligand-dependent Wnt signaling activity.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

View full text Add to dashboard Cite

Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/β-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/β-catenin pathway antagonists-secreted frizzledrelated protein 1 and Wnt inhibitory factor 1-on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia. Response to tyrosine kinase inhibitors was analyzed in secreted frizzled-related protein 1 and Wnt inhibitory factor 1 stably transfected K562 cells. Experiments were repeated using a tetracycline-inducible expression system, confirming previous results. In addition, response to tyrosine kinase inhibitor treatment was also analyzed using the secreted frizzled-related protein 1 expressing, BCR-ABL positive MEG01 cell line, in the presence and absence of a secreted frizzled-related protein 1 inhibitor. Our data suggests that total cellular β-catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total β-catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. We suggest that Wnt antagonists carry the potential to be exploited in designing new agents and strategies for the advanced and resistant forms of chronic myeloid leukemia.

show abstract

Wnt signaling in cancer stem cells and colon cancer metastasis

Cited by 159 publications

References 90 publications

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Lgr5+CD44+EpCAM+ Strictly Defines Cancer Stem Cells in Human Colorectal Cancer

Ubiquitin-Specific Peptidase 22 Contributes to Colorectal Cancer Stemness and Chemoresistance via Wnt/β-Catenin Pathway

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

Contact Info

Product

Resources

About