Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition

Evdokimova, Valentina; Tognon, Cristina E.; Ng, Tony; Ruzanov, Peter; Melnyk, Natalya; Fink, Dieter; Sorokin, Alexey V.; Ovchinnikov, Lev P.; Davicioni, Elai; Triche, Timothy J.; Sorensen, Poul H.

doi:10.1016/j.ccr.2009.03.017

Cited by 414 publications

(445 citation statements)

References 40 publications

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“…This supports the notion that EMT-inducing factors reduce cell proliferation, 28,62 and circulating tumor cells (CTCs) with enhanced Twist1 need to downregulate Twist1 before regaining the ability to proliferate and form macrometastases. 63 We propose that during development of radioresistance in CaP, and possibly other types of cancer, reversion of EMT is necessary for initiation of cell proliferation.…”

Section: Discussionsupporting

confidence: 79%

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

et al. 2014

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Fractionated ionizing radiation combined with surgery or hormone therapy represents the first-choice treatment for medium to high-risk localized prostate carcinoma. One of the main reasons for the failure of radiotherapy in prostate cancer is radioresistance and further dissemination of surviving cells. In this study, exposure of four metastasis-derived human prostate cancer cell lines (DU145, PC-3, LNCaP and 22RV1) to clinically relevant daily fractions of ionizing radiation (35 doses of 2 Gy) resulted in generation of two radiation-surviving populations: adherent senescent-like cells expressing common senescenceassociated markers and non-adherent anoikis-resistant stem cell-like cells with active Notch signaling and expression of stem cell markers CD133, Oct-4, Sox2 and Nanog. While a subset of the radiation-surviving adherent cells resumed proliferation shortly after completion of the irradiation regimen, the non-adherent cells started to proliferate only on their reattachment several weeks after the radiation-induced loss of adhesion. Like the parental non-irradiated cells, radiation-surviving re-adherent DU145 cells were tumorigenic in immunocompromised mice. The radiation-induced loss of adhesion was dependent on expression of Snail, as siRNA/shRNA-mediated knockdown of Snail prevented cell detachment. On the other hand, survival of the non-adherent cells required active Erk signaling, as chemical inhibition of Erk1/2 by a MEK-selective inhibitor or Erk1/2 knockdown resulted in anoikis-mediated death in the non-adherent cell fraction. Notably, whereas combined inhibition of Erk and PI3K-Akt signaling triggered cell death in the non-adherent cell fraction and blocked proliferation of the adherent population of the prostate cancer cells, such combined treatment had only marginal if any impact on growth of control normal human diploid cells. These results contribute to better understanding of radiation-induced stress response and heterogeneity of human metastatic prostate cancer cells, document treatment-induced plasticity and phenotypically distinct cell subsets, and suggest the way to exploit their differential sensitivity to radiosensitizing drugs in overcoming radioresistance. Cell Death and Differentiation (2015) 22, 898-911; doi:10.1038/cdd.2014.97; published online 11 July 2014Prostate carcinoma (CaP) is the most frequent type of cancer in men, and the sixth cause of cancer-associated death in men worldwide. 1 Despite the advances in diagnosis and therapy of CaP, the mortality has remained almost unchanged for the last decades. Currently, the most successful treatment for localized CaP is prostatectomy with postoperative fractionated radiotherapy, significantly improving metastasis-free and overall survival, where the median of a 15-year survival is around 47% of patients. 2,3 The rest of the patients develop a metastatic disease that is incurable due to the resistance of CaP to androgen ablation, radiotherapy and chemotherapy. Therefore, understanding the mechanisms of radioresistance and chemoresista...

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Section: Discussionsupporting

confidence: 79%

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

et al. 2014

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“…We confirmed TWIST1 mRNA and protein upregulation during EMT, 9 but observed downregulation in cell lines representing early stages of cancer development (Figures 1b and c; Supplementary Figure 1a). This was unexpected, as the upregulation of TWIST1 has been demonstrated in a variety of human cancers, 3 including breast cancer.…”

Section: Resultssupporting

confidence: 71%

“…10 Stable transduction of MCF-10ANeoT cells with Y-box binding protein 1 YB-1 (MCF-10ANeoT-YB-1, termed YB-1 in figures) induced EMT. 9 YB-1 is a known transcriptional and translational regulator, 18 and is a downstream target of TWIST1. 19 Figure 1a shows a schematic summary of the cell lines used.…”

Section: Resultsmentioning

confidence: 99%

Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Vislovukh

Meng

et al. 2012

Oncogene

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TWIST1 is a highly conserved basic helix-loop-helix transcription factor that promotes epithelial --mesenchymal transition (EMT). Its misregulation has been observed in various types of tumors. Using the MCF-10A-series of cell lines that recapitulate the early stages of breast cancer formation and EMT, we found TWIST1 to be upregulated during EMT and downregulated early in carcinogenesis. The TWIST1 3 0 UTR contains putative regulatory elements, including miRNA target sites and two cytoplasmic polyadenylation elements (CPE). We found that miR-580, CPEB1, and CPEB2 act as negative regulators of TWIST1 expression in a sequence-specific and additive/cooperative manner.

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“…Increased levels of Snail and Y-box factor-1 (YB-1) have been shown in invasive breast epithelial cells (Evdokimova et al 2009). YB-1 promotes the expression of Snail, N-cadherin, and TWIST.…”

Section: Regulation Of Translation In Emtmentioning

confidence: 99%

Post-transcriptional regulation in cancer progression

Jewer

Findlay

Postovit

2012

J. Cell Commun. Signal.

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The microenvironment acts as a conduit for cellular communication, delivering signals that direct development and sustain tissue homeostasis. In pathologies such as cancer, this integral function of the microenvironment is hijacked to support tumor growth and progression. Cells sense the microenvironment via signal transduction pathways culminating in altered gene expression. In addition to induced transcriptional changes, the microenvironment exerts its effect on the cell through regulation of posttranscriptional processes including alternative splicing and translational control. Here we describe how alternative splicing and protein translation are controlled by microenvironmental parameters such as oxygen availability. We also emphasize how these pathways can be utilized to support processes that are hallmarks of cancer such as angiogenesis, proliferation, and cell migration. We stress that cancer cells respond to their microenvironment through an integrated regulation of gene expression at multiple levels that collectively contribute to disease progression.

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Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition

Cited by 414 publications

References 40 publications

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

Radiotherapy-induced plasticity of prostate cancer mobilizes stem-like non-adherent, Erk signaling-dependent cells

Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Post-transcriptional regulation in cancer progression

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