Emerging Mechanisms by which EMT Programs Control Stemness

Wilson, Molly M.; Weinberg, Robert A.; Lees, Jacqueline A.; Guen, Vincent J.

doi:10.1016/j.trecan.2020.03.011

Cited by 163 publications

(137 citation statements)

References 40 publications

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“…As there are several molecular pathways exploited by breast cancer cells with EMT, along with those residing in a stem-like state [ 22 ], these mechanisms were also confirmed in our study. In particular, it was observed that CSCs are closely related to EMT, and that EMT is likely to be critical in tumor invasion and metastasis [ 17 , 23 ]. Furthermore, CSCs are responsible for tumorigenesis-associated processes, as these cells display increased resistance to therapy, even promoting tumors post-treatment relapse [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it was observed that CSCs are closely related to EMT, and that EMT is likely to be critical in tumor invasion and metastasis [ 17 , 23 ]. Furthermore, CSCs are responsible for tumorigenesis-associated processes, as these cells display increased resistance to therapy, even promoting tumors post-treatment relapse [ 17 ]. Thus, identification of transcriptional markers for these two pathways in order to understand resistance towards some of the most prevalently used therapies for treatment of breast cancer will greatly benefit breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…This process can be snatched by cancer cells, being frequently linked with resistance to apoptosis, acquisition of cancer stem cell characteristics, and drug resistance [ 16 ]. EMT programs/processes/mechanisms promote CSC stemness in many epithelial tissues; therefore, understanding these relationships may highlight different therapeutic vulnerabilities that can be further exploited in clinical practice [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

Groza

Braicu

Jurj

et al. 2020

Cancers

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Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing, rendering it unpredictable and causing more harm than ever before on an annual basis. Alterations of coding and noncoding genes are related to tumorigenesis and breast cancer progression. In this study, several key genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features were identified. EMT and CSCs are two key mechanisms responsible for self-renewal, differentiation, and self-protection, thus contributing to drug resistance. Therefore, understanding of the relationship between these processes may identify a therapeutic vulnerability that can be further exploited in clinical practice, and evaluate its correlation with overall survival rate. To determine expression levels of altered coding and noncoding genes, The Cancer Omics Atlas (TCOA) are used, and these data are overlapped with a list of CSCs and EMT-specific genes downloaded from NCBI. As a result, it is observed that CSCs are reciprocally related to EMT, thus identifying common signatures that allow for predicting the overall survival for breast cancer genes (BRCA). In fact, common CSCs and EMT signatures, represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c, are deemed useful as prognostic biomarkers for BRCA. Therefore, by mapping changes in gene expression across CSCs and EMT, suggesting a cross-talk between these two processes, we have been able to identify either the most common or specific genes or miRNA markers associated with overall survival rate. Thus, a better understanding of these mechanisms will lead to more effective treatment options.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

Groza

Braicu

Jurj

et al. 2020

Cancers

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show abstract

“…Substantial in vitro and in vivo studies have provided convincing evidence supporting CSCs as the critical cause of cancer initiation, growth, metastasis, and treatment resistance in cancers [20][21][22][23][24] . CSCs were also found to exhibit characteristics of an EMT, a process known to enable cancer cell dissemination and metastasis to other organs [35][36][37][38][39][40][41] . Additionally, significant and convincing evidence shows that inducing EMT in cancer cells confers cancer stem cell-like characteristics, which promote their metastatic and tumor-initiating abilities [37,38] .…”

Section: Pcscsmentioning

confidence: 99%

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Safa

2020

JCMT

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Metastasis, tumor progression, and chemoresistance are the major causes of death in patients with pancreatic ductal adenocarcinoma (PDAC). Tumor dissemination is associated with the activation of an epithelial-tomesenchymal transition (EMT) process, a program by which epithelial cells lose their cell polarity and cell-tocell adhesion, and acquire migratory and invasive abilities to become mesenchymal stem cells (MSC). These MSCs are multipotent stromal cells capable of differentiating into various cell types and trigger the phenotypic transition from an epithelial to a mesenchymal state. Therefore, EMT promotes migration and survival during cancer metastasis and confers stemness features to particular subsets of cells. Furthermore, a major problem limiting our ability to treat PDAC is the existence of rare populations of pancreatic cancer stem cells (PCSCs) or cancer-initiating cells in pancreatic tumors. PCSCs may represent sub-populations of tumor cells resistant to therapy which are most crucial for driving invasive tumor growth. These cells are capable of regenerating the cellular heterogeneity associated with the primary tumor when xenografted into mice. Therefore, the presence of PCSCs has prognostic relevance and influences the therapeutic response of tumors. PCSCs express markers of cancer stem cells (CSCs) including CD24, CD133, CD44, and epithelial specific antigen as well as the drug transporter ABCG2 grow as spheroids in a defined growth medium. A major difficulty in studying tumor cell dissemination and metastasis has been the identification of markers that distinguish metastatic cancer cells from cells that are normally circulating in the bloodstream or at sites where these cells metastasize. Evidence highlights a linkage between CSC and EMT. In this review, The current understanding of the PCSCs, signaling pathways regulating these cells, PDAC heterogeneity, EMT mechanism, and links between EMT and metastasis in PCSCs

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“…As spheroid culture has been shown to enrich for cells with stem cell properties, these findings suggest that intrinsic stemness-independent of exogenous treatments-may be associated with a more mesenchymal phenotype. The relationship between the EMT and stemness is well documented 12,32 , but there is growing evidence that stemness and EMT are not inextricably linked. For example, the EMT-promoted transcription factor PRRX1 suppresses stemness in breast cancer cells 33 .…”

Section: Brca1 Loss Promotes Emt-independent Stemness In Mosementioning

confidence: 99%

Transcriptional heterogeneity of stemness phenotypes in the ovarian epithelium

Carter

Cook

McCloskey

et al. 2020

Preprint

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The ovarian surface epithelium (OSE) is a monolayer of epithelial cells covering the surface of the ovary. During ovulation, the OSE is ruptured to allow release of the oocyte. This wound is quickly repaired, but mechanisms of this repair are poorly understood. The contribution of tissue-resident stem cells in the homeostasis of several epithelial tissues is widely accepted, such as the intestinal epithelium, airway epithelium, and skin, but their involvement in OSE maintenance is unclear. While putative stem cell populations in the OSE have been described, how they are regulated is poorly defined. We show that traits associated with stem cells (stemness) can be increased in OSE following exposure to the cytokine TGFB1, overexpression of the transcription factor Snai1 , or deletion of Brca1 . By assessing the gene expression profiles of these populations, we show that stemness is often linked to mesenchymal-associated gene expression and higher activation of ERK signalling, but it is not consistently dependent on their activation. Expression profiles of these populations are extremely context specific, suggesting that stemness may not correspond to a single, distinct population, but rather is a heterogenous state that can possibly emerge from diverse environmental cues. Together, these findings support that the OSE may not require distinct stem cell populations for long-term maintenance, and may achieve this through transient dedifferentiation into a stem-like state./

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Emerging Mechanisms by which EMT Programs Control Stemness

Cited by 163 publications

References 40 publications

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic

Epithelial-mesenchymal transition: a hallmark in pancreatic cancer stem cell migration, metastasis formation, and drug resistance

Transcriptional heterogeneity of stemness phenotypes in the ovarian epithelium

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