FAM83D promotes epithelial-mesenchymal transition, invasion and cisplatin resistance through regulating the AKT/mTOR pathway in non-small-cell lung cancer

ConclusionsOur results suggest a role of FAM83D in NSCLC development. In addition, our results  indicate that NSCLC patients exhibiting FAM83D overexpression are likely to benefit from AKT and/or mTOR inhibitor treatment.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research

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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
In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the freq...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusion PPLELC is uncommon but distinct subtype of NSCLC with unique clinicop athologic characteristics that tends to affect young nonsmoking patients, without significant predilection for sex and with strong association with Epstein-Barr virus (EBV) infection. Histology and immunohistochemistry are the main diagnostic methods. Rare or no driver gene mutations were found in t he common oncogenes such as EGFR mutations and ALK gene rearrangement, implying that the mutagenesis of these genes was not involved in the tumorigenesis of PPLELC. PD-1 and PD-L1 may be potential therapeutic targets for PPLELC. The patients a...
Source: Chinese Journal of Lung Cancer - Category: Cancer & Oncology 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
Abstract Therapies for lung cancer patients initially illicit desirable responses, but the presence of hypoxia and drug resistant cells within tumors ultimately lead to treatment failure. Disulfiram (DSF) is an FDA approved, copper chelating agent that can target oxidative metabolic frailties in cancer vs. normal cells and be repurposed as an adjuvant to cancer therapy. Clonogenic survival assays showed that DSF (50-150 nM) combined with physiological levels of Cu (15 μM CuSO4) was selectively toxic to H292 NSCLC cells versus normal human bronchial epithelial cells (HBEC). Furthermore, cancer cell toxicity ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
Contributors : Rui Li ; Stephanie L Ong ; Linh M Tran ; Zhe Jing ; Zhi L Huang ; Bin Liu ; Gina Lee ; Ramin Salehi-Rad ; Kostyantyn Krysan ; Paul C Pagano ; Manash K Paul ; Shili Xu ; Harvey R Herschman ; Steven M DubinettSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensChronic inflammation facilitates tumor development. However, the underlying mechanism is largely unknown. Here, we found IL-1 β, a critical cytokine in lung tumor progression, induces epithelial-to-mesenchymal (EMT) in non-small cell lung cancer (NSCLC) cells. Chronic IL-1β exposure leads to “EMT memory,...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
This study reports herein that gemcitabine synergizes with RASSF1A, silencing to increase the IAP-2 expression, which in turn not only interferes with cell proliferation but also promotes cell migration. This contributes to the aggressive behavior of RASSF1A-depleted cells, as confirmed by a combined knockdown of IAP-2 and RASSF1A. Conversely, paclitaxel does not increase the IAP-2 expression but limits the invasiveness of RASSF1A-depleted cells, presumably by rescuing microtubule stabilization. Overall, these data provide a functional insight that supports the prognostic value of RASSF1 gene methylation on survival of ear...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This study aimed to investigate how bevacizumab, a vascular endothelial growth factor A (VEGFA) neutralizing antibody applied in clinic, affects the tight junction protein CLDN5 and subsequently influences tumor cell invasion and potential metastasis. Western-blot, quantitative real-time polymerase chain reaction (q-PCR), immunofluorescence and immunohistochemistry revealed that low-dose bevacizumab up-regulated CLDN5, whereas high-dose bevacizumab down-regulated CLDN5. Cell migration, invasion and permeation assay demonstrated that high-dose bevacizumab enhanced the migration, invasion and permeation abilities of human um...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
Abstract Cancer stem cells (CSCs) play an important role in cancer treatment resistance and disease progression. Identifying an effective anti-CSC agent may lead to improved disease control. We used CSC-associated gene signatures to identify drug candidates that may inhibit CSC growth by reversing the CSC gene signature. Thiostrepton, a natural cyclic oligopeptide antibiotic, was the top-ranked candidate. In non-small-cell lung cancer (NSCLC) cells, thiostrepton inhibited CSC growth in vitro and reduced protein expression of cancer stemness markers, including CD133, Nanog and Oct4A. In addition, metastasis-associa...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Publication date: Available online 20 August 2019Source: Pharmacological ResearchAuthor(s): Hong-Yuan Lu, Yu-Xin Zu, Xiao-Wen Jiang, Xiao-Tong Sun, Tian-Yi Liu, Ruo-Lan Li, Qiong Wu, Ying-Shi Zhang, Qing-Chun ZhaoAbstractAcquired drug-resistant non-small cell lung cancer (NSCLC) has strong proliferation ability and is prone to epithelial-mesenchymal transition (EMT) and subsequent metastasis. Notch pathway mediates cell survival and EMT and is involved in the induction of multidrug resistance (MDR). ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 we found before. However, the effects of ZLDI-8 on resista...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
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