Dataset Information

Nogo-B receptor is required for stabilizing TGF-? type I receptor and promotes the TGF-?1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer.

ABSTRACT: Background and Objective: Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear. Methods: TGF-?1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-?1-induced NSCLC metastasis were studied by gain- and loss-of-function assays both in vitro and in vivo. The underlying mechanisms were studied using molecular biology assays. Results: We found that knockdown of NgBR inhibited TGF-?1-induced cell migration and invasion in NSCLC cells. In contrast, NgBR overexpression promoted TGF-?1-induced EMT of A549 cells. Mechanically, we found that knockdown of NgBR facilitated ubiquitination and degradation of T?RI, leading to downregulation of T?RI expression in NSCLC cells. Moreover, we confirmed a positive correlation between NgBR and T?RI in NSCLC tissues. Conclusions: Our findings provide a novel role of NgBR in modulating TGF-?1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients.

SUBMITTER: Wu D

PROVIDER: S-EPMC7778533 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Nogo-B receptor is required for stabilizing TGF-β type I receptor and promotes the TGF-β1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer.

Wu Donghua D Zhao Baofeng B Song Yang Y Chi Xinming X Fu Hailu H Guan Tiantong T Zhang Liyuan L Yang Xueguang X Hu Ke K Huang Rong R Jin Xiaomeng X Miao Qing Robert QR Shao Shujuan S

Journal of Cancer 20210101 3

<b>Background and Objective:</b> Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear. <b>Methods:</b> TGF-β1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-β1-induced NSCLC metastasis were studied b ...[more]

PMID: 33403029

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Project description:An altered liver microenvironment characterized by a dysregulated extracellular matrix (ECM) supports the development and progression of hepatocellular carcinoma (HCC). The development of experimental platforms able to reproduce these physio-pathological conditions is essential in order to identify and validate new therapeutic targets for HCC. The aim of this work was to validate a new in vitro model based on engineering three-dimensional (3D) healthy and cirrhotic human liver scaffolds with HCC cells recreating the micro-environmental features favoring HCC. Healthy and cirrhotic human livers ECM scaffolds were developed using a high shear stress oscillation-decellularization procedure. The scaffolds bio-physical/bio-chemical properties were analyzed by qualitative and quantitative approaches. Cirrhotic 3D scaffolds were characterized by biomechanical properties and microarchitecture typical of the native cirrhotic tissue. Proteomic analysis was employed on decellularized 3D scaffolds and showed specific enriched proteins in cirrhotic ECM in comparison to healthy ECM proteins. Cell repopulation of cirrhotic scaffolds highlighted a unique up-regulation in genes related to epithelial to mesenchymal transition (EMT) and TGFβ signaling. This was also supported by the presence and release of higher concentration of endogenous TGFβ1 in cirrhotic scaffolds in comparison to healthy scaffolds. Fibronectin secretion was significantly upregulated in cells grown in cirrhotic scaffolds in comparison to cells engrafted in healthy scaffolds. TGFβ1 induced the phosphorylation of canonical proteins Smad2/3, which was ECM scaffold-dependent. Important, TGFβ1-induced phosphorylation of Smad2/3 was significantly reduced and ECM scaffold-independent when pre/simultaneously treated with the TGFβ-R1 kinase inhibitor Galunisertib. In conclusion, the inherent features of cirrhotic human liver ECM micro-environment were dissected and characterized for the first time as key pro-carcinogenic components in HCC development.

Dataset Information

Nogo-B receptor is required for stabilizing TGF-? type I receptor and promotes the TGF-?1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer.

Publications

Nogo-B receptor is required for stabilizing TGF-β type I receptor and promotes the TGF-β1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer.

Similar Datasets

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