Cancer stem cells and their role in metastasis

Shiozawa, Yusuke; Nie, Biao; Pienta, Kenneth J.; Morgan, Todd M.; Taichman, Russell S.

doi:10.1016/j.pharmthera.2013.01.014

Cited by 218 publications

(181 citation statements)

References 138 publications

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“…The plasticity of CSCs improves their chances to survive in a foreign environment, where growth factors and signaling molecules differ from those at the primary cancer site [66]. Plasticity may also facilitate the EMT process, possibly a key event in the early phase of metastasis [4]. This possibility will be discussed in more detail.…”

Section: Cancer Stem Cells and Metastasismentioning

confidence: 97%

“…It has been hypothesized that the CSCs are responsible for the generation of new tumors distant form the primary site, based on the demonstration that CSCs present in human breast cancers are able to generate both primary tumors in the breast of mice as well as secondary tumors in the lung [4,64]. In another, CSCs from human pancreatic tumors were placed in the pancreas of mice and shown to generate distant liver metastases [4]. Different CSC populations may be responsible for the different tumor sites.…”

Section: Cancer Stem Cells and Metastasismentioning

confidence: 99%

“…The ability of cells to migrate is a vital process during normal development and tumor cells appear to have acquired this capacity [4]. Cells in normal adult tissues maintain migratory capacity through their ability to generate an EMT process.…”

Section: Cancer Stem Cells and Metastasismentioning

confidence: 99%

“…Loss of microRNA-124 (miR-124), which normally regulates cell proliferation, has been shown to promote glioma formation. Thus, miRNAs may participate in the activation of CSC-like activities [4]. Krueppel-like factor 4 (KLF4)is a protein which is used to 'reprogram' somatic cells into stem cell-like cells.…”

Section: Doi: 107243/2052-6199-1-7mentioning

confidence: 99%

“…A recent hypothesis-proposes that distinct cells in a tumor exist that have a cancer-initiating capacity. These so-called cancer stem cells (CSCs) are thought to be the source of tumor heterogeneity during evolution of the tumor and the primary targets of selective forces that lead to improved growth properties and the capacity to metastasize [1,4]. CSCs have been proposed to originate from normal stem cells or more differentiated cells and possess or have reacquired distinctive capacities, including self-renewal and the ability to give rise to more differentiated cell types [5].…”

Section: Introductionmentioning

confidence: 99%

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Cancer stem cells and addicted cancer cells

Logtenberg¹,

Boonstra²

2013

Oncol Discov

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Advanced tumors represent a genetically heterogeneous population of cells, which compromise subpopulations with distinct properties. Research indicates that a specific population of cells within the heterogeneous population contain stem cell-like properties. These 'cancer stem cells' are much like normal stem cells and have the capacity to self-renew, sustain the entire cancerous tissues and provide a reservoir of cells for recurrence after therapy and drug resistance. Cancer stem cells can arise from normal, adult stem cells, from progenitor cells or from fully matured cell types. They are likely generated by the process of epithelial-mesenchymal transition, through which differentiated cells acquire stem-cell like properties. This process potentially underlies the mechanism by which metastases evolve. Furthermore, mutations may render cancer cells dependent on the activity of one or more specific signaling pathways in the cell. This phenomenon is termed 'oncogene addiction' and represents the Achilles' heel of the cancer cell. As the concept of oncogene addiction in tumor cells proves to be very complex, additional models have been proposed to account for the variations in pathway dependencies and their intricate interactions. The combined knowledge concerning cancer stem cells, oncogene addiction and drug therapy resistance may lead to the identification of new avenues to improved drug strategies that address tumor heterogeneity and mechanisms of escape.

show abstract

Section: Cancer Stem Cells and Metastasismentioning

confidence: 97%

Section: Cancer Stem Cells and Metastasismentioning

confidence: 99%

Section: Cancer Stem Cells and Metastasismentioning

confidence: 99%

Section: Doi: 107243/2052-6199-1-7mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cancer stem cells and addicted cancer cells

Logtenberg¹,

Boonstra²

2013

Oncol Discov

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Endothelin‐converting enzyme‐1c promotes stem cell traits and aggressiveness in colorectal cancer cells

et al. 2019

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Endothelin-1 is a mitogenic peptide that activates several proliferation, survival, and invasiveness pathways. The effects of endothelin-1 rely on its activation by endothelin-converting enzyme-1 (ECE1), which is expressed as four isoforms with different cytoplasmic N termini. Recently, isoform ECE1c has been suggested to have a role in cancer aggressiveness. The N terminus of ECE1c is phosphorylated by protein kinase CK2 (also known as casein kinase 2), and this enhances its stability and promotes invasiveness in colorectal cancer cells. However, it is not known how phosphorylation improves stability and why this is correlated with increased aggressiveness. We hypothesized that CK2 phosphorylation protects ECE1c from N-terminal ubiquitination and, consequently, from proteasomal degradation. Here, we show that lysine 6 is the bona fide residue involved in ubiquitination of ECE1c and its mutation to arginine (ECE1c K6R ) significantly impairs proteasomal degradation, thereby augmenting ECE1c stability, even in the presence of the CK2 inhibitor silmitasertib. Furthermore, colorectal cancer cells overexpressing ECE1c K6R displayed enhanced cancer stem cell (CSC) traits, including increased stemness gene expression, chemoresistance, self-renewal, and colony formation and spheroid formation in vitro, as well as enhanced tumor growth and metastasis in vivo. These findings suggest that CK2-dependent phosphorylation enhances ECE1c stability, promoting an increase in CSC-like traits. Therefore, phospho-ECE1c may be a biomarker of poor prognosis and a potential therapeutic target for colorectal cancer.

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A three‐dimensional microenvironment alters CD73 expression in cervical cancer

Iser

Mello

Davies

et al. 2021

Cell Biochemistry & Function

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Stem‐like cells (CSCs) have a tumour‐initiating capacity and play critical role in tumour metastasis, relapse and resistance to therapy. The ectoenzyme CD73, encoded by the NT5E gene, which catalyses the hydrolysis of AMP into adenosine, has been associated to an immunosuppressive tumour microenvironment, tumour cell adhesion and migration. Therefore, we investigated the expression and activity of CD73 in sphere‐forming cells from cervical cancer in comparison to monolayer cells in vitro. In addition, in silico analysis was performed to determine the expression of CD73 and other members of purinergic signalling in CSC‐like population derived from different tumour types in comparison to monolayer cells. CD73 protein expression levels and functionality in SiHa cells were analysed by flow cytometry and enzymatic assay, respectively. In silico investigation was performed through the analysis of seven datasets from different tumour types using GEO database. In vitro analysis showed a decreased CD73 protein expression and enzymatic activity in cervical spheres, when compared to monolayers. In addition, when sphere‐derived cells are re‐plated as monolayer culture, the CD73 expression and activity are restored. Supporting the in vitro results, in silico analysis showed that three‐dimensional spheres derived from cervical, thyroid and breast cancer presented decreased expression of CD73, when compared to their adherent counterparts. The decreased expression of CD73 in sphere‐derived cells or CSC‐enriched population reinforce its important role in cell adhesion, tumour spreading ability and metastasis, suggesting CD73 as potential target to be further investigated in cervical cancer.

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Cancer stem cells and their role in metastasis

Cited by 218 publications

References 138 publications

Cancer stem cells and addicted cancer cells

Cancer stem cells and addicted cancer cells

Endothelin‐converting enzyme‐1c promotes stem cell traits and aggressiveness in colorectal cancer cells

A three‐dimensional microenvironment alters CD73 expression in cervical cancer

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