VPS33B suppresses lung adenocarcinoma metastasis and hemoresistance to Cisplatin

Publication date: Available online 8 January 2020Source: Genes &DiseasesAuthor(s): Zhen Liu, Jiahao Liu, Yang Li, Hao Wang, Zixi Liang, Xiaojie Deng, Qiaofen Fu, Weiyi Fang, Ping XuAbstractThe presence of VPS33B in tumors has rarely been reported. Downregulated VPS33B protein expression is an unfavorable factor that promotes the pathogenesis of lung adenocarcinoma (LUAD). Overexpressed VPS33B was shown to reduce the migration, invasion, metastasis, and chemoresistance of LUAD cells to cisplatin (DDP) in vivo and in vitro. Mechanistic analyses have indicated that VPS33B first suppresses epidermal growth factor receptor (EGFR) Ras/ERK signaling, which further reduces the expression of the oncogenic factor c-Myc. Downregulated c-Myc expression reduces the rate at which it binds the p53 promoter and weakens its transcription inhibition; therefore, decreased c-Myc stimulates p53 expression, leading to decreased epithelial-to-mesenchymal transition (EMT) signal. NESG1 has been shown to be an unfavorable indicator of non-small-cell lung cancer (NSCLC). Here, NESG1 was identified as an interactive protein of VPS33B. In addition, NESG1 was found to exhibit mutual stimulation with VPS33B via reduced RAS/ERK/c-Jun-mediated transcription repression. Knockdown of NESG1 activated EGFR/Ras/ERK/c-Myc signaling and further downregulated p53 expression, which thus activated EMT signaling and promoted LUAD migration and invasion. Finally, we observed that nicotine suppressed VPS33B expressi...
Source: Genes and Diseases - Category: Genetics & Stem Cells Source Type: research

Related Links:

This study aimed to unveil profiles of mutant proteins expressed in lung adenocarcinomas of 36 patients harboring representative driver EGFR mutations (Ex19del, nine; L858R, nine; no Ex19del/L858R, 18). Surprisingly, the orthogonal partial least squares discriminant analysis performed for identified mutant proteins demonstrated the profound differences in distance among the different EGFR mutation groups, suggesting that cancer cells harboring L858R or Ex19del emerge from cellular origins different from L858R/Ex19del-negative cells. Weighted gene coexpression network analysis, together with over-representative analysis, id...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Background and objective Leptomeningeal metastasis (LM) are a severe complication of non-small cell lung cancer (NSCLC), and normally accompanied by poor prognosis. For the patients with targetable mutations, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment, but the acquired TKI resistance is inextricable. The aim of this study is to analyze the different gene mutation spectrum and mutation frequency of the cerebrospinal fluid (CSF) and plasma in NSCLC patients with LM, and screen out the drug-resistant mutations so as to guide the choice of treatment accurately. Methods ...
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology Source Type: research
Authors: Zhuang MQ, Li J, Han X, Su KL, Hao GJ, Han JQ Abstract Lung cancer mortality remains high, and only approximately 15% of patients with non-small cell lung cancer survive for more than five years. The purpose of this research was to investigate the prognostic value and biological functions of G protein regulated inducer of neuritis outgrowth 1(GPRIN1) in lung cancer. We used the Kaplan-Meier method to analyze the correlation between GPRIN1 and overall survival, and performed Cox regression to determine whether GPRIN1 might be an independent predictive factor for lung adenocarcinoma prognosis. qRT-PCR and We...
Source: Journal of Biological Regulators and Homeostatic Agents - Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research
In conclusion, EpCAM+CD73+ cells are a rare novel epithelial progenitor cell in human lung. Importantly, re-emergence of CD73 in lung adenocarcinoma enriched in negative immune checkpoint molecules may serve as a novel therapeutic target. PMID: 32726135 [PubMed - as supplied by publisher]
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research
In this study we elucidated the molecular mechanisms of resistance in osimertinib-resistant NCI-H1975/OSIR cells. We showed that NCI-H1975/OSIR cells underwent epithelial-mesenchymal transition (EMT), which conferred sensitivity to the GPX4 inhibitor 1S, 3R-RSL3 to induce ferroptotic cell death. The EMT occurrence resulted from osimertinib-induced upregulation of TGFβ2 that activated SMAD2. On the other hand, we revealed that NCI-H1975/OSIR cells were highly dependent on NF-κB pathway for survival, since treatment with the NF-κB pathway inhibitor BAY 11-7082 or genetic silence of p65 caused much greater ce...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
Datta Epidemiologic studies have shown that vast majority of lung cancers (85–90%) are causally linked to tobacco smoking. Although much information has been gained about the effects of smoking on various signaling pathways, little is known about how deregulation of miRNAs leads to activation of oncogenes and inhibition of tumor suppressor genes in non-small cell lung cancer (NSCLC). Our previous study showed that smoking inhibits TGF-β-induced tumor suppressor functions through downregulation of Smad3 in lung cancer cells. In order to understand the upstream mechanism of downregulation of Smad3 by s...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This study was designed to investigate the reversal effect of astragalus polysaccharides (APS) on gefitinib resistance (GR) and to elucidate the underlying mechanisms. PC9 and HCC827 lung cancer cells were stimulated by TGF-β1 to develop EMT-associated GR cells. Cell proliferation, migration and apoptosis assays were used to confirm the effect of gefitinib on GR cells and the therapeutic effect of APS on GR cells after knockdown and over-expression of related signaling pathways. Reverse transcription polymerase chain reaction, western blotting, and immunofluorescent staining assays were used to evaluate the expression...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Triptolide inhibits epithelial‑mesenchymal transition and induces apoptosis in gefitinib‑resistant lung cancer cells. Oncol Rep. 2020 Mar 10;: Authors: Li F, Cui H, Jin X, Gong X, Wang W, Wang J Abstract The epidermal growth factor receptor‑tyrosine kinase inhibitor (EGFR‑TKI), gefitinib, is used widely to treat non‑small cell lung cancer (NSCLC) with EGFR‑activating mutations. Unfortunately, the acquired drug resistance promoted by epithelial‑mesenchymal transition (EMT) markedly limits the clinical effects and remains a major barrier to a cure. Our previous isobaric tags for relative an...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Somatic alterations in the epidermal growth factor receptor gene (EGFR) result in aberrant activation of kinase signaling and occur in ∼15% of non-small cell lung cancers (NSCLC). Patients diagnosed with EGFR-mutant NSCLC have good initial clinical response to EGFR tyrosine kinase inhibitors (EGFR TKIs), yet tumor recurrence is common and quick to develop. Mechanisms of acquired resistance to EGFR TKIs have been studied extensively over the past decade. Great progress has been made in understanding two major routes of therapeutic failure: additional genomic alterations in the EGFR gene and activation of alternative kin...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
RARITAN, NJ, March 10, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for JNJ-61186372 (JNJ-6372) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy. JNJ-6372 is an EGFR-mesenchymal epithelial transition factor (MET) bispecific antibody that targets activating and resistant EGFR and MET mutations and amplifications.[1]...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
More News: Adenocarcinoma | Cancer | Cancer & Oncology | Epithelial Cancer | Genetics | Lung Cancer | Nicotine | Non-Small Cell Lung Cancer | Study