Expression data of mammary epithelial cells during the epithelial-mesenchymal transition
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE43495 | GEO | 2013/09/09
SECONDARY ACCESSION(S): PRJNA186603
REPOSITORIES: GEO
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Project description:The EMT program allows epithelial cells to become endowed with motility, invasiveness and stem cell traits. We investigated difference in signaling networks that are differentially utilized in EMTed and non-EMTed cells, thereby identifying therapeutic targets that are unique to EMT/cancer stem cells. We expressed the EMT transcription factors, Twist, Snail and Slug in HMLE human mammary epithelial cells, and compared their gene expression with parental cells. We identified kinases that are more differentially regulated between the epithelial and mesenchymal cell state.
2013-09-09 | E-GEOD-43495 | biostudies-arrayexpress
Project description:Malignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal, survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis. The complete database comprised the expression measurements of 54 675 genes for PC-3/Mc (n=3) and PC-3/S (n=3)
2012-07-23 | E-GEOD-24868 | biostudies-arrayexpress
Project description:Malignant progression in cancer has been associated with the emergence of populations of tumor-initiating cells (TIC) endowed with capabilities for unlimited self-renewal, survival under stress and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by the genetic program known as epithelialmesenchymal transition (EMT) may be an essential step in the evolution of neoplastic cells into fully metastatic populations. A widely accepted paradigm is that EMT potentiates tumor cell self-renewal and metastatic behaviour. Here we describe a cellular model in which a clonal population enriched in TIC expresses a genetic program distinct from a second population with traits of stable EMT, and in which both populations cooperate for enhanced local invasiveness and metastasis. Induction of the TIC-enriched population to undergo EMT by several stimuli or by constitutive overexpression of the transcription factor SNAI1 engaged a mesenchymal program while suppressing the CSC program. This suggests that TIC and EMT, contrary to current paradigms, correspond to alternative states. Furthermore, diffusible factors secreted by the population with EMT traits also induced mesenchymal reprogramming of the population enriched in CSCs. Local invasiveness in vitro and lung colonization in vivo of the TIC-enriched population was enhanced by co-injection with the EMT-trait population, and expanded the range of organs to which it metastasized. Thus, in our model, relatively stable TIC and EMT phenotypes reflect alternative genetic programs expressed by distinct clonal populations. We also suggest that dynamic cooperation between tumor subpopulations displaying either TIC or EMT traits may be a general mechanism driving local invasiveness and metastasis.
2012-07-24 | GSE24868 | GEO
Project description:Epithelial-mesenchymal transition (EMT) is a highly conserved morphogenic process defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. EMT is associated with increased aggressiveness, invasiveness, and metastatic potential in carcinoma cells. To assess the contribution of extracellular vesicles following EMT, we conducted a proteomic analysis of shed microvesicles released from Madin-Darby canine kidney (MDCK) cells, and MDCK cells transformed with oncogenic H-Ras (21D1 cells).
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Project description:Neuroblastoma (NB) with MYCN amplification is a highly metastatic tumor in children, and unraveling the key players involved in MYCN-induced invasion may identify new targets for therapy. Epithelial-mesenchymal transition (EMT) plays a critical role in promoting metastasis and we have recently determined that MYCN interacts with LSD1, a histone de-methylase flavin oxidase, which has been found to promote EMT. We show here that LSD1 affects motility and invasiveness of NB cells through transcription modulation of the metastasis suppressor NDRG1, N-Myc Downstream-Regulated Gene 1. LSD1 co-localizes with MYCN at the promoter region of the NDRG1 gene and it inhibits its expression. LSD1-inhibition relieves NDRG1 repression induced by MYCN with concomitant block of motility and invasiveness of NB cells, and such effects were recapitulated by overexpressing NDRG1. Moreover, we found that low NRDG1 and high LSD1 levels in NB patients were associated with poor survival. These data suggest that LSD1 inhibition may knock down the ability of MYCN-amplified Neuroblastomas to metastasize. Our findings elucidate a mechanism of how MYCN/LSD1 control motility and invasiveness of NB cells through transcription regulation of NDRG1 expression and they suggest that pharmacological targeting of LSD1 could inhibit the NB metastatic process.
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Project description:Background: The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT). Methods: We used xenograft models of human cancer cells in immunocompromised mice, profiling the harvested tumors separately with species-specific probes and computationally analyzing the results. Results: Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature that prominently includes many EMT markers, among them the transcription factor Slug, fibronectin, and α-SMA. We found that human, but not mouse, cells express the signature and Slug is the only upregulated EMT-inducing transcription factor. The signature is also present in samples from many publicly available cancer gene expression datasets, suggesting that it is produced by the cancer cells themselves in multiple cancer types, including nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting that the signature is triggered by contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported. Conclusions: The known, precise and consistent gene composition of this cancer mesenchymal transition signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics. 18 neuroblastoma tumor samples were profiled for gene expression twice by human U133A 2.0 and mouse 430A 2.0 arrays.
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2023-08-02 | GSE207772 | GEO
Project description:The epithelial-mesenchymal transition (EMT) is a developmental program that is co-opted by tumor cells to aid in their embarking on the metastatic cascade. Tumor cells that undergo EMT are known to be endowed by, amongst other traits, heightened resistance to chemotherapy. Despite a clear understanding of the role played by the EMT program in conferring cells with these aggressive traits, there are currently no therapeutic avenues specifically targeting the program. Here we show that treatment of mesenchymal-like breast cancer cells with eribulin, an FDA-approved drug for the treatment of advanced breast cancers, leads to a mesenchymal-epithelial transition (MET), accompanied by a loss of metastatic propensity and sensitization of tumor cells to subsequent rounds of chemotherapy. We uncover a novel alternate mechanism of action that provides evidence for eribulin pretreatment as a viable clinical mechanism of MET induction that curtails metastatic progression and the evolution of therapy resistance.
2023-08-02 | GSE207767 | GEO
Project description:The epithelial-mesenchymal transition (EMT) is a developmental program that is co-opted by tumor cells to aid in their embarking on the metastatic cascade. Tumor cells that undergo EMT are known to be endowed by, amongst other traits, heightened resistance to chemotherapy. Despite a clear understanding of the role played by the EMT program in conferring cells with these aggressive traits, there are currently no therapeutic avenues specifically targeting the program. Here we show that treatment of mesenchymal-like breast cancer cells with eribulin, an FDA-approved drug for the treatment of advanced breast cancers, leads to a mesenchymal-epithelial transition (MET), accompanied by a loss of metastatic propensity and sensitization of tumor cells to subsequent rounds of chemotherapy. We uncover a novel alternate mechanism of action that provides evidence for eribulin pretreatment as a viable clinical mechanism of MET induction that curtails metastatic progression and the evolution of therapy resistance.
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Project description:The epithelial-mesenchymal transition (EMT) is a developmental program that is co-opted by tumor cells to aid in their embarking on the metastatic cascade. Tumor cells that undergo EMT are known to be endowed by, amongst other traits, heightened resistance to chemotherapy. Despite a clear understanding of the role played by the EMT program in conferring cells with these aggressive traits, there are currently no therapeutic avenues specifically targeting the program. Here we show that treatment of mesenchymal-like breast cancer cells with eribulin, an FDA-approved drug for the treatment of advanced breast cancers, leads to a mesenchymal-epithelial transition (MET), accompanied by a loss of metastatic propensity and sensitization of tumor cells to subsequent rounds of chemotherapy. We uncover a novel alternate mechanism of action that provides evidence for eribulin pretreatment as a viable clinical mechanism of MET induction that curtails metastatic progression and the evolution of therapy resistance.
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