Regulation of the protein stability of EMT transcription factors

Dı́az, Vı́ctor M.; Viñas-Castells, Rosa; Herreros, Antonio Garcı́a de

doi:10.4161/19336918.2014.969998

Cited by 84 publications

(72 citation statements)

References 142 publications

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“…Consistent with these findings, we found that the protein levels of TGF-β RII, Smad2, Smad3, phospho-Smad2/3 markedly decreased in HMGA2-siRNA transfected cells, which suggested that down-regulation of HMGA2 inhibited the activation of TGF-β/Smad pathway in prostate cancer cells. Additionally, the core EMT regulatory factors, such as Snail, Slug and Twist have been proved to be inversely correlated with the expression of E-cadherin (De Craene and Berx 2013; Dalvi et al 2009;Lander et al 2011;Diaz et al 2014). Therefore, further studies are needed to address whether HMGA2 has an effect on those transcriptional repressors.…”

Section: Discussionmentioning

confidence: 94%

Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

Shi

Tang

et al. 2016

J Biosci

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The high mobility group protein A2 (HMGA2) has been demonstrated as an architectural transcription factor that is associated with pathogenesis of many malignant cancers; however, its role in prostate cancer cells remains largely unknown. To explore whether HMGA2 participates in the development and progression of prostate cancer, small interfering RNA (siRNA) targeted on human HMGA2 was transfected to suppress the HMGA2 expression in prostate cancer PC3 and DU145 cells, and then the cellular biology changes after decreased the expression of HMGA2 was examined. Our results showed that knockdown of HMGA2 markedly inhibited cell proliferation; this reduced cell proliferation was due to the promotion of cell apoptosis as the Bcl-xl was decreased, whereas Bax was up-regulated. In addition, we found that HMGA2 knockdown resulted in reduction of cell migration and invasion, as well as repressed the expression of matrix metalloproteinases (MMPs) and affected the occurrence of epithelial-mesenchymal transition (EMT) in both cell types. We further found that decreased HMGA2 expression inhibited the transforming growth factor-beta (TGF-beta)/Smad signalling pathway in cancer cells. In conclusion, our data indicated that HMGA2 was associated with apoptosis, migration and invasion of prostate cancer, which might be a promising therapeutic target for prostate cancer.

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Section: Discussionmentioning

confidence: 94%

Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

Shi

Tang

et al. 2016

J Biosci

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“…While we saw an increase in TWIST1 and SLUG gene expression in the Rag/MKR Ctrl tumors compared to the Rag/WT Ctrl tumors, we did not see a significant difference in the protein levels of these genes between the Rag/MKR Ctrl and Rag/WT Ctrl tumors. This may be in part due to the short half-life of the TWIST and SNAIL transcription factor family proteins that are rapidly polyubiquitinated and degraded by the proteasome in cells (Diaz, et al 2014). These mesenchymal factors are essential markers of EMT, a biological process in which polarized-epithelial cells undergo various changes to take on a mesenchymal phenotype.…”

Section: Discussionmentioning

confidence: 99%

EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

Zelenko

Gallagher

Antoniou

et al. 2016

Endocrine-Related Cancer

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Type 2 Diabetes (T2D) is associated with increased cancer risk and cancer-related mortality. Data herein show that we generated an immunodeficient hyperinsulinemic mouse by crossing the Rag1−/− mice, which have no mature B or T lymphocytes, with the MKR mouse model of T2D to generate the Rag1−/− (Rag/WT) and Rag1−/−/MKR+/+ (Rag/MKR) mice. The female Rag/MKR mice are insulin resistant and have significantly higher non-fasting plasma insulin levels compared to the Rag/WT controls. Therefore, we used these Rag/MKR mice to investigate the role of endogenous hyperinsulinemia on human cancer progression. In this study we show that hyperinsulinemia in the Rag/MKR mice increases the expression of mesenchymal transcription factors, TWIST1 and ZEB1, and increases the expression of the angiogenesis marker, vascular endothelial growth factor A (VEGFA). We also show that silencing the insulin receptor (IR) in the human LCC6 cancer cells leads to decreased tumor growth and metastases, suppression of mesenchymal markers Vimentin, SLUG, TWIST1, and ZEB1, suppression of angiogenesis markers, VEGFA and VEGFD, and re-expression of the epithelial marker, E-cadherin. The data in this paper demonstrate that IR knockdown in primary tumors partially reverses the growth promoting effects of hyperinsulinemia as well as highlighting the importance of the insulin receptor signaling pathway in cancer progression, and more specifically in epithelial-mesenchymal transition.

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“…The expression of several other genes will be turned on including those encoding VEGF-B, the receptor for VEGF-B, Flt1, and the metalloproteinases MMP-9 and MMP-1. Several transcription factors, such as Slug [31], Snail [33][34][35][36][37], Twist1 [35,38], and the ZEB family of transcriptions factors, will also be activated, and their roles are slowly being elucidated [35,39,40]. Corroborating the idea of dedifferentiation of cancer cells to take on stem-like properties as cancer progresses, these transcription factors are known regulators of embryonic morphogenesis, yet are highly expressed not only in all cancer cells but specifically in metastatic cells, but also are documented to play various roles in facilitating EMT [32].…”

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confidence: 99%

Involvement of Mesenchymal Stem Cells in Cancer Progression and Metastases

Chang¹,

Schwertschkow²,

Nolta³

et al. 2015

CCDT

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Mesenchymal stem/stromal cells (MSCs) are known to be the helpers for the healing of tissue damage, often referred to as ambulatory cells. However, MSCs are also recruited by cancer cells to similarly aid in tumor growth and progression. In this review, some of the key steps in cancer progression and metastases are described including the various steps in which MSCs participate and may play important roles. MSCs aid in cancer cells' ability to evade immune attack, while promoting tumor angiogenesis, even being counter-acting against chemotherapeutics and other drugs used to fight various cancers. Furthermore, MSCs participate in many of the crucial steps in invasion and metastasis, including stimulating the epithelial-mesenchymal transition (EMT) and induction of stem-like properties that allow cancer stem cells to increase their survivability through the circulation. These steps are described in detail. Differences between circulating tumor cells (CTCs) and cancer stem cells (CSCs) are discussed, along with descriptions of the formation of a pre-metastatic niche, the role of exosomes from both cancer cells and MSCs in metastasis and tumor reseeding (self-seeding). More and more, MSCs are being proposed as a promising tumor targeting drug-delivery tool. In order to fulfill this promise, further understanding of the precise roles that MSCs play in the process of cancer metastases must be achieved, in attempting to create remedies that will improve the outcome of available therapeutics.

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Regulation of the protein stability of EMT transcription factors

Cited by 84 publications

References 142 publications

Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

Silencing of HMGA2 promotes apoptosis and inhibits migration and invasion of prostate cancer cells

EMT reversal in human cancer cells after IR knockdown in hyperinsulinemic mice

Involvement of Mesenchymal Stem Cells in Cancer Progression and Metastases

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