Cancer stem cells: a model in the making

Marotta, Lauren L Campbell; Polyák, Kornélia

doi:10.1016/j.gde.2008.12.003

Cited by 107 publications

(100 citation statements)

References 52 publications

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“…Support for this concept in EOC is presented by our in vivo analyses of EOC tumor samples, as described below. In this regard, tumor growth potential may depend on the presence of CSCs that have the ability to self-renew, and thereby repopulate the tumor mass (Fodde, 2009;Jinawath et al, 2009;Jordan, 2009;Marotta and Polyak, 2009). In this context, tumor cells positive for both of these two stem cell markers (that is, the majority of cells in both the PA-1 and IGROV1 cell lines) would represent CSC candidates.…”

Section: Sub-population Of Eoc Cells Co-expresses Lin28 and Oct4mentioning

confidence: 99%

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

2010

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Section: Sub-population Of Eoc Cells Co-expresses Lin28 and Oct4mentioning

confidence: 99%

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

2010

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“…This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs. cellular transformation | inflammation | cancer stem cells equilibrium C ancer stem cells (CSCs; also called tumor-initiating cells) are a highly tumorigenic cell type that exist as a minority population within tumors and have been hypothesized to be key drivers of cancer (1)(2)(3)(4)(5)(6). CSCs have been isolated from developmentally diverse tumors and established cell lines via cellsurface markers (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), and they are defined by the following properties: self-renewal under nondifferentiation conditions, ability to differentiate into nonstem cancer cells (NSCCs), and high tumorigencity upon injection in immunodeficient mice.…”

mentioning

confidence: 99%

Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion

Iliopoulos

Hirsch

Wang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

587

555

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Tumors are often heterogeneous, being composed of multiple cell types with different phenotypic and molecular properties. Cancer stem-like cells (CSCs) are a highly tumorigenic cell type found in developmentally diverse tumors or cancer cell lines, and they are often resistant to standard chemotherapeutic drugs. The origins of CSCs and their relationships to nonstem cancer cells (NSCCs) are poorly understood. In an inducible breast oncogenesis model, CSCs are generated from nontransformed cells at a specific time during the transformation process, but CSC formation is not required for transformation. MicroRNA profiles indicate that CSCs and NSCCs are related, but different cell types arising from a common nontransformed population. Interestingly, medium from the transformed population stimulates NSCCs to become CSCs, and conversion of NSCCs to CSCs occurs in mouse xenografts. Furthermore, IL6 is sufficient to convert NSCCs to CSCs in genetically different breast cell lines, human breast tumors, and a prostate cell line. Thus, breast and prostate CSCs and NSCCs do not represent distinct epigenetic states, and these CSCs do not behave as or arise from classic stem cells. Instead, tumor heterogeneity involves a dynamic equilibrium between CSCs and NSCCs mediated by IL6 and activation of the inflammatory feedback loop required for oncogenesis. This dynamic equilibrium provides an additional rationale for combining conventional chemotherapy with metformin, which selectively inhibits CSCs. cellular transformation | inflammation | cancer stem cells equilibrium

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“…These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells. C ancer stem cells (CSCs; also called tumor-initiating cells) are a highly tumorigenic cell type that exist as a minority population within tumors, and have been hypothesized to be play a pivotal role in cancer (1)(2)(3)(4)(5)(6). CSCs from developmentally diverse tumors and established cell lines have been isolated by using cell-surface markers.…”

mentioning

confidence: 99%

An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state

Polytarchou

Iliopoulos

Struhl

2012

Proc. Natl. Acad. Sci. U.S.A.

137

111

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Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs. Aside from the previously identified miR-200 family, these include the miR-15/16 (miR-16, miR-15b) and miR-103/107 (miR-103, miR-107) families as well as miR-145, miR-335, and miR-128b. Interestingly, these miRNAs affect common target genes that encode the Bmi1 and Suz12 components of the polycomb repressor complexes as well as the DNA-binding transcription factors Zeb1, Zeb2, and Klf4. Conversely, expression of the CSC-modulating miRNAs is inhibited by Zeb1 and Zeb2. There is an inverse relationship between the levels of CSC-regulating miRNAs and their respective targets in samples from triple-negative breast cancer patients, providing evidence for the relevance of these interactions in human cancer. In addition, combinatorial overexpression of these miRNAs progressively attenuates the growth of CSCs derived from triple-negative breast cancers. These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells.

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Cancer stem cells: a model in the making

Cited by 107 publications

References 52 publications

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Pluripotency factors Lin28 and Oct4 identify a sub-population of stem cell-like cells in ovarian cancer

Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion

An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state

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