Faculty Opinions recommendation of The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse.

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.

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Colorectal cancer stem cells: Characterization and functional analysis

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4124 ◽

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.

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

Anticancer Research ◽

10.21873/anticanres.12285 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 3

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

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SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1

10.21203/rs.3.rs-29004/v1 ◽

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.

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The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽

10.3390/cancers13081833 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1833

Author(s):

Tsai-Tsen Liao ◽

Wei-Chung Cheng ◽

Chih-Yung Yang ◽

Yin-Quan Chen ◽

Shu-Han Su ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Cell Motility ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Cell Stiffness ◽

Mesenchymal Transition ◽

Cytoskeletal Dynamics ◽

Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

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PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer

Biomaterials Science ◽

10.1039/d1bm00160d ◽

2021 ◽

Author(s):

Yingru Zhang ◽

Chunpu Li ◽

Ru Jia ◽

Ruixuan Gao ◽

Yiyang Zhao ◽

...

Keyword(s):

Colorectal Cancer ◽

Stem Cells ◽

Amino Acid ◽

Cancer Stem Cells ◽

Drug Release ◽

Signaling Pathway ◽

Water Solubility ◽

Sustained Drug Release ◽

Colorectal Cancer Stem Cells ◽

Micelle System

A new nano-micelle system with better water solubility and sustained drug release effect, targeting colorectal cancer stem cells, effectively inhibits the growth and metastasis of colorectal cancer via the Wnt/β-catenin signaling pathway.

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