Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer

Li, Aiwei; Zhu, Xiaoyan; Wang, Chanjuan; Yang, Shuo; Qiao, Yan; Qu, Rui; Zhang, Jie

doi:10.1038/s41598-019-41660-w

Cited by 40 publications

(30 citation statements)

References 45 publications

(58 reference statements)

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“…Given the histological features (epithelial source/origin) of urothelial carcinomas, the EMT may be closely related to the occurrence and progression of BC. The EMT may also play a role in BC cell tolerance to treatment 39,40…”

Section: Discussionmentioning

confidence: 99%

<p>The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells</p>

Zhou¹,

Liu²,

Deng³

et al. 2019

OTT

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BackgroundDespite progress achieved in bladder cancer (BC) treatment, the prognosis of patients with advanced BC (ie, metastasized from the bladder to other organs) is poor. Although mortality in cases of low-grade BC is rare, the treatment, such as a radical cystectomy, often has a serious impact on the quality of life. Thus, research is needed to identify more effective treatment strategies and this work is aiming to examine the potential application of combination of radiofrequency ablation (RFA) and SB435142, a inhibitor of transforming growth factor β (TGFβ)/Smad pathway.MethodsBC cells were transplanted into nude mice (thymusdeficiency Bal B/c) to form subcutaneous tumors. The mice with subcutaneous tumors were then treated with RFA and oral administration of SB431542, an inhibitor of TGFβ/Smad signaling pathway. The antitumor effect of RFA was measured by tumor proliferation curves and micro-positron emission computed tomography (micro-PET). The effect of SB431542 on epithelial–mesenchymal transition (EMT) related regulators in subcutaneous tumor tissues formed by BC cells were examined by quantitative real-time polymerase chain reaction (qPCR) experiments.ResultsThe SB431542 treatment enhanced the antitumor effect of RFA on subcutaneous growth of BCs. SB431542 also decreased EMT-related regulators in subcutaneous tumor tissues formed by BC cells in nude mice.ConclusionSB431542 enhances the effect of RFA on BC.

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Section: Discussionmentioning

confidence: 99%

<p>The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells</p>

Zhou¹,

Liu²,

Deng³

et al. 2019

OTT

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“…Immunofluorescence (IF) staining was performed as described previously 46,47 . Immunohistochemistry and semiquantitative scoring techniques were performed as described previously 48 . More details are included in the Supplementary Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

ELTD1 facilitates glioma proliferation, migration and invasion by activating JAK/STAT3/HIF-1α signaling axis

Shen

Wang

et al. 2019

Sci Rep

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The upregulation of ELTD1 ([epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing 1] on chromosome 1) in tumor cells has been reported in several types of cancer and correlates with poor cancer prognosis. However, the role of ELTD1 in glioma progression remains unknown. In this study, we examined ELTD1 expression levels in human glioma cell lines and in sixteen human gliomas of different grades. The molecular effects of ELTD1 in glioma cells were measured using quantitative polymerase chain reaction (qRT-PCR), Western blotting, Cell proliferation assays, Matrigel migration and invasion assays and brain orthotopic xenografts. We found that high expression levels of ELTD1 were positively associated with cancer progression and poor prognosis in human glioma. Mechanistically, ELTD1 activated the JAK/STAT3/HIF-1α signaling axis and p-STAT3 bound with HIF-1α. Taken together, our data provide a plausible mechanism for ELTD1-modulated glioma progression and suggest that ELTD1 may represent a potential therapeutic target in the prevention and therapy of glioma.

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“…Phosphorylation of NDRG1, a regulator of the cytoskeleton that has been implicated in cancer migration and invasion [ 30 , 31 ], was dramatically downregulated following the suppression of CIT expression. We further validated these findings using a phospho-NDRG1 antibody (Fig.…”

Section: Resultsmentioning

confidence: 99%

CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies

et al. 2021

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Introduction Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes. Results Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. We use this strategy to test functional dependencies of 820 transcript isoforms that are gained in gastric cancer (GC). We identify a subset of GC-gained transcript isoform dependencies, and of these, we validate CIT kinase as a novel GC dependency. We further show that some genes express isoforms with opposite functions. Specifically, we find that the tumour suppressor ZFHX3 expresses an isoform that has a paradoxical oncogenic role that correlates with poor patient outcome. Conclusions Our work finds isoform-specific phenotypes that would not be identified using current loss-of-function approaches that are not designed to target specific transcript isoforms.

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Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer

Cited by 40 publications

References 45 publications

<p>The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells</p>

<p>The TGF-β/Smad Pathway Inhibitor SB431542 Enhances The Antitumor Effect Of Radiofrequency Ablation On Bladder Cancer Cells</p>

ELTD1 facilitates glioma proliferation, migration and invasion by activating JAK/STAT3/HIF-1α signaling axis

CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies

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