Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications

Serrano-Gómez, Silvia J.; Maziveyi, Mazvita; Alahari, Suresh K.

doi:10.1186/s12943-016-0502-x

Cited by 562 publications

(429 citation statements)

References 140 publications

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“…E-cadherin degradation by netrin pretreatment enhances migratory ability of hUCB-MSCs [50]. The reduction of E-cadherin expression during cell migration can be controlled by epigenetic transcriptional regulation and post-transcriptional modification of transcription for the CDH1 gene [51]. Our results investigating the effect of high glucose on E-cadherin and its epigenetic regulators showed that high glucose decreased the expression of E-cadherin via increasing the expressions of EZH2 and Snail.…”

Section: Discussionmentioning

confidence: 98%

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

Choi

Lee

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glucose plays an important role in stem cell fate determination and behaviors. However, it is still not known how glucose contributes to the precise molecular mechanisms responsible for stem cell migration. Thus, we investigate the effect of glucose on the regulation of the human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) migration, and analyze the mechanism accompanied by this effect. Methods: Western blot analysis, wound healing migration assays, immunoprecipitation, and chromatin immunoprecipitation assay were performed to investigate the effect of high glucose on hUCB-MSC migration. Additionally, hUCB-MSC transplantation was performed in the mouse excisional wound splinting model. Results: High concentration glucose (25 mM) elicits hUCB-MSC migration compared to normal glucose and high glucose-pretreated hUCB-MSC transplantation into the wound sites in mice also accelerates skin wound repair. We therefore elucidated the detailed mechanisms how high glucose induces hUCB-MSC migration. We showed that high glucose regulates E-cadherin repression through increased Snail and EZH2 expressions. And, we found high glucose-induced reactive oxygen species (ROS) promotes two signaling; JNK which regulates γ–secretase leading to the cleavage of Notch proteins and PI3K/Akt signaling which enhances GSK-3β phosphorylation. High glucose-mediated JNK/Notch pathway regulates the expression of EZH2, and PI3K/Akt/GSK-3β pathway stimulates Snail stabilization, respectively. High glucose enhances the formation of EZH2/Snail/HDAC1 complex in the nucleus, which in turn causes E-cadherin repression. Conclusion: This study reveals that high glucose-induced ROS stimulates the migration of hUCB-MSC through E-cadherin repression via Snail and EZH2 signaling pathways.

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Section: Discussionmentioning

confidence: 98%

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

Choi

Lee

et al. 2018

Cell Physiol Biochem

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“…Cancer cells were endowed with increased motility and invasiveness during this process. E-cadherin, as a critical molecular feature of EMT, was downregulated and indicated as a tumor suppressive role in various carcinomas [25,28]. Zeng et al [29] elucidated that loss of E-cadherin expression or function could initiate the activation of transcription factors which are associated with EMT, finally resulting in cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

Zhang

Zhou

et al. 2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…At protein level, no significant differences were detected in the protein expression of E-cadherin and vimentin by MDA-MB-231 cells (Fig. 3b, c) this may be attributed to the post-translational modification of E-cadherin and vimentin by MDA-MB-231 [21,22]. Our present results suggested a Fig.…”

Section: Secretome Of Tals Isolated From Breast Tumor Microenvironmenmentioning

confidence: 47%

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

et al. 2016

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Epithelial-mesenchymal transition (EMT) is an essential process in breast cancer metastasis. The aim of the present study was to determine the role of secretions of tumor-associated leukocytes (TALs) isolated from negative and positive lymph nodes (nLNs and pLNs, respectively) breast cancer patients in regulating EMT mechanism and the associated signaling pathways. We found an increased infiltration of TALs, which was associated with downregulation of E-cadherin and over-expression of vimentin in the breast carcinoma tissues of pLNs as compared to nLNs patients and normal breast tissues obtained from healthy volunteers during mammoplasty. Furthermore, TALs isolated from pLNs breast cancer patients secreted an elevated panel of cytokines by up to 2-5-fold when compared with those isolated from nLNs patients. Secretome of TALs of pLNs possessed higher TARC, IGF-1, IL-3, TNF-β, IL-5, G-CSF, IL-4, and IL-1α with more than a fivefold compared to those of nLNs. Using the human breast cancer cell lines MCF-7 and MDA-MB-231, we found that cytokines secreted by TALs isolated from nLNs and pLNs breast cancer patients promoted EMT via upregulation of TGF-β and vimentin and downregulation of E-cadherin at messenger RNA (mRNA) levels in both cell lines and at protein level in MCF-7. While TGF-β is over-expressed by MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. The downstream TGF-β signaling transcription factors, Snail, Slug, and Twist, known to be associated with EMT mechanism were over-expressed by MCF-7 and MDA-MB-231 seeded in media conditioned by secretome of TALs isolated from nLNs and pLNs breast cancer patients. Acquisition of EMT in MCF-7 cells is mechanistically attributed to the activation of EGFR and NF-κB/p65 signaling which are significantly highly expressed by MCF-7 cells seeded in media conditioned by secretome of TALs isolated from pLNs compared to nLNs patients. Overall, this study provides implications of secretome of TALs and activated EGFR and NF-κB/p65 in EMT process that may be considered a therapeutic strategy to inhibit lymph node metastasis in breast cancer patients.

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Regulation of epithelial-mesenchymal transition through epigenetic and post-translational modifications

Cited by 562 publications

References 140 publications

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

High Glucose-Induced Reactive Oxygen Species Stimulates Human Mesenchymal Stem Cell Migration Through Snail and EZH2-Dependent E-Cadherin Repression

CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics

Secretome of tumor-associated leukocytes augment epithelial-mesenchymal transition in positive lymph node breast cancer patients via activation of EGFR/Tyr845 and NF-κB/p65 signaling pathway

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