scholarly journals Transglutaminase 2 Regulates Self-renewal and Stem Cell Marker of Human Colorectal Cancer Stem Cells

2018 ◽  
Vol 38 (2) ◽  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Transglutaminase 2 ◽  
Stem Cell Marker ◽  
Cell Marker ◽  
Human Colorectal Cancer ◽  
Self Renewal ◽  
Colorectal Cancer Stem Cells

scholarly journals SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1

2020 ◽  
Author(s):  
Cong Tian ◽  
Tingyuan Lang ◽  
Jiangfeng Qiu ◽  
Kun Han ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Drug Target ◽  
Human Colorectal Cancer ◽  
Protein Levels ◽  
Colorectal Cancer Cells ◽  
And Migration ◽  
Colorectal Cancer Stem Cells

Abstract Background: Cancer stem cells have been recognized as an important drug target, however, the mechanisms underlying the maintenance of cancer stem cells have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 could be a target for eradicating cancer stem cells remains elusive.Methods: Human colorectal cancer cell lines HCT-116 and HT-29 and primary human colorectal cancer cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels were examined by qRT-PCR and western blot, respectively. Sphere formation and transwell assay were employed for examination of sphere-forming and migration capacities. The tumorigenicity was examined by xenograft model. The transcriptional activities of the promoters were examined by luciferase reporter assay. Co-immunoprecipitation assay was used to test protein-protein interaction. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± s.d. and the significance was determined by Student’s t-test.Results: SKP1 is upregulated in colorectal cancer stem cells and predicts poor prognosis of colon cancer patients. Overexpression of SKP1 promotes the sphere-forming and migration capacities of colorectal cancer stem cells, and upregulates the expression of cancer stem cell markers. In contrast, SKP1 depletion produces the opposite effects. SKP1 strengthens YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of colorectal cancer cells. SKP1 suppresses RASSF1 at both mRNA and protein levels and overexpression of RASSF1 abolished the effect of SKP1.Conclusion: In summary, our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of colorectal cancer stem cells. Our works thus revealed a novel underlying mechanism of colorectal cancer stem cell maintenance and suggested a novel drug target for eradicating colorectal cancer stem cells.

scholarly journals TRIB3 Interacts With β-Catenin and TCF4 to Increase Stem Cell Features of Colorectal Cancer Stem Cells and Tumorigenesis

2019 ◽  
Vol 156 (3) ◽  
pp. 708-721.e15 ◽  
Author(s):  
Fang Hua ◽  
Shuang Shang ◽  
Yu-wei Yang ◽  
Hai-zeng Zhang ◽  
Tian-lei Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Colorectal Cancer Stem Cells

scholarly journals Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303381989226
Author(s):  
Yu-Shui Ma ◽  
Wen Li ◽  
Yu Liu ◽  
Yi Shi ◽  
Qin-Lu Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Human Life ◽  
Research Direction ◽  
Current Treatment ◽  
New Drugs ◽  
Colorectal Cancer Stem Cells ◽  
Cancer Tissues

As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.

Colorectal cancer stem cells: Characterization and functional analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4124-4124
Author(s):  
T. Yeung ◽  
J. Wilding ◽  
W. Bodmer
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Stem Cell ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tumour Growth ◽  
Colorectal Cancer Cell Lines ◽  
Colorectal Cancer Stem Cells

4124 Background: Cancer stem cells are defined as cells within a tumour that are able to self-renew and differentiate into all cell lineages within that tumour. With our extensive panel of colorectal cell lines, our aims are: 1) To characterise and isolate cancer stem cells based on stem cell markers, morphological appearances and the ability to form multiple lineages; 2) To understand how cancer stem cells drive tumour growth and progression. Methods: 1) Fluorescent Activated Cell Sorting (FACS); 2) In vitro soft agar clonogenic and Matrigel differentiation assays; 3) In vivo tumourigenic NOD/SCID mice assay; 4) Confocal immunofluorescence imaging. Results: 1) A subpopulation of cells can differentiate into crypt-like megacolonies, retaining the ability to self-renew and differentiate. SW1222 cell line forms heterogeneous colonies when single cells are plated in Matrigel. Megacolonies can both self-renew and form terminally differentiated small colonies, whereas small colonies cannot form megacolonies. Megacolonies develop crypt-like structures and increase their expression of differentiation markers (CDX-1, CK-20) over time. Experiments are currently under way to confirm that cells from megacolonies are able to initiate tumours in NOD/SCID mice. Some cell lines retain the ability to differentiate into both neuroendocrine and epithelial lineages. 2) CD44+CD24+ enriches for the cancer stem cell population. Colorectal cancer cell lines HCT116, HT29, LS180, LS174T and SW1222 express both CD44 and CD24. The CD44+CD24+ subpopulation is the most clonogenic. In SW1222, CD44+CD24+ cells enrich for megacolonies and can reform all four CD44/CD24 subpopulations. 3) Hypoxia reduces differentiation, increases stem-like phenotype and enhances clonogenicity. Hypoxia increases the proportion of undifferentiated colorectal cancer cells when plated on Matrigel and increases clonogenicity. Conclusions: 1) Colorectal cancer cell lines contain subpopulations of cells that have the ability to self-renew, differentiate and drive tumour growth, and may be characterised by their cell surface markers and colony morphology. 2) CD44+CD24+ can be used as markers for colorectal cancer stem cells. 3) Hypoxia increases the stem-like phenotype of cancer cells, reduces differentiation and increases clonogenicity. No significant financial relationships to disclose.

scholarly journals Author Correction: KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiong Li ◽  
Bo Yu ◽  
Peng Deng ◽  
Yingduan Cheng ◽  
Yongxin Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Stem Cells

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals miR-221 Targets QKI to Enhance the Tumorigenic Capacity of Human Colorectal Cancer Stem Cells

2019 ◽  
Vol 79 (20) ◽  
pp. 5151-5158 ◽  
Author(s):  
Junko Mukohyama ◽  
Taichi Isobe ◽  
Qingjiang Hu ◽  
Takanori Hayashi ◽  
Takashi Watanabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Stem Cells

scholarly journals KDM3 epigenetically controls tumorigenic potentials of human colorectal cancer stem cells through Wnt/β-catenin signalling

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jiong Li ◽  
Bo Yu ◽  
Peng Deng ◽  
Yingduan Cheng ◽  
Yongxin Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Gene Transcription ◽  
Target Gene ◽  
Histone Demethylases ◽  
Human Colorectal Cancer ◽  
Tumorigenic Potential ◽  
Colorectal Cancer Stem Cells ◽  
Target Gene Transcription

Abstract Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription. The depletion of KDM3 inhibits tumorigenic growth and chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly erases repressive H3K9me2 marks, but also helps to recruit histone methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target gene transcription. Our results suggest that KDM3 is a critical epigenetic factor in Wnt signalling that orchestrates chromatin changes and transcription in human colorectal CSCs, identifying potential therapeutic targets for effective elimination of CSCs.

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