Ontology highlight
ABSTRACT:
PROVIDER: PRJNA564798 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10095291.fastq.gz | Fastqsanger.gz | |||
| SRR10095292.fastq.gz | Fastqsanger.gz | |||
| SRR10095293.fastq.gz | Fastqsanger.gz | |||
| SRR10095294.fastq.gz | Fastqsanger.gz | |||
| SRR10095295.fastq.gz | Fastqsanger.gz |
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Project description:Expression data of preneoplastic lung neuroendocrine cells and L-Myc signature
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Project description:Enhanced RAF/MEK/ERK signaling plays an obligatory role in many different types of cancer. Although genetic lesions promoting its aberrant activation are found in lung adenocarcinoma (LADC), the biological role of this pathway is not well documented in small cell lung cancer (SCLC). Here we explored the role of this pathway in SCLC and the broader class of tumors with neuroendocrine (NE) differentiation by introducing a constitutively active form of Fibroblast growth factor receptor 1 (Fgfr1) together with biallelic inactivation of Rb1 and Trp53 in mouse lung. Our data show that FGFR1 expression primarily results in LADC but also in NE tumors depending on the cell-of-origin. FGFR1 activation selectively promoted NE bronchial lesions in a novel lung cell subpopulation, whereas it impaired progression of typical central SCLC initiated from CGRP-expressing NE cells, which is believed to be the most prominent cell-of-origin of SCLC. Strikingly, FGFR1 activation was well tolerated by K14-expressing cells that were efficiently transformed into SCLC and other NE lesions. Taken together, our results indicate that FGFR1 can serve either as driver or suppressor of distinct lung cancer subtypes depending on the cell-of-origin, which should be taken into account when considering FGFR1 as a therapeutic target.
2020-03-27 | GSE132759 | GEO
Project description:Lung cancer is the leading cause of cancer related deaths, worldwide. Fibroblast growth factor receptor 1 (FGFR1) gene amplification is one of the most prominent and potentially targetable genetic alterations in squamous cell lung cancer (SQCLC). Highly selective tyrosine kinase inhibitors have been developed to target FGFR1, however, resistance mechanisms originally existing in patients or acquired throughout treatment have limited treatment efficiency in clinical trials, so far. In this study, we performed a wide-scale phosphoproteomic mass spectrometry analysis to explore signaling pathways that lead to FGFR1 inhibition resistance in lung cancer cells with intrinsic, induced and mutational resistance. We identified a CD44/AKT signaling axis as a new and common mechanism of resistance to FGFR1 inhibition in lung cancer. Co-inhibition of AKT or CD44 synergistically sensitized intrinsic and induced resistant cells to FGFR1 inhibition. Furthermore, strong CD44 expression was significantly correlated to AKT activation in squamous cell lung cancer patients. Collectively, our phosphoproteomic analysis of FGFR1 inhibitor resistant lung cancer cells promotes a large data library of resistance associated phosphorylation patterns and proposes a common resistance pathway consisting of CD44 and AKT activation. Examination of CD44/AKT activation could help to predict response to FGFR1 inhibition and combination with AKT inhibitors might path the way for an effective therapy of FGFR1 dependent lung cancer patients in case of treatment resistance.
2022-08-12 | PXD025389 | Pride
Project description:Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis.
2019-05-14 | PXD013583 | JPOST Repository
Project description:Basic studies on preneoplastic lesions are important to determine the molecular alterations that take place in early steps of lung carcinogenesis. Little is known about the molecular events preceding the development of lung cancer in the context of an inflammatory environment. In this study we report the generation of a chemical-induced lung carcinogenesis mouse model in the presence of silicotic chronic inflammation. Silica-induced lung inflammation, strongly promoted incidence of lung cancer in mice treated with NDMA, a carcinogen found in tobacco smoke. Histological and molecular analysis revealed that permanent inflammation contributed to lung tumorigenesis through the adquisition of preneoplastic changes in lung epithelial cells. Inflammatory milieu increased the expression of PDCD1, TGFβ-1, MCP-1, LAG3, and Foxp3 and the presence of regulatory T cells within preneoplastic lesions. In addition concomitant chronic inflammation changed the K-ras mutational profile of the generated tumors from Q61R to G12D transition. In summary, these data identify early molecular mechanisms underlying lung carcinogenesis in an inflammatory context at different steps, providing a novel approach for the identification of drivers from preneoplastic to neoplastic lesions Gene expression profile was analyzed in 11 individual lesions (8 adenomas and 3 adenocarcinomas) from the NDMA-silica treated mice and 5 lesions (2 adenomas, and 3 adenocarcinomas) from NDMA-only treated mice
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Project description:Basic studies on preneoplastic lesions are important to determine the molecular alterations that take place in early steps of lung carcinogenesis. Little is known about the molecular events preceding the development of lung cancer in the context of an inflammatory environment. In this study we report the generation of a chemical-induced lung carcinogenesis mouse model in the presence of silicotic chronic inflammation. Silica-induced lung inflammation, strongly promoted incidence of lung cancer in mice treated with NDMA, a carcinogen found in tobacco smoke. Histological and molecular analysis revealed that permanent inflammation contributed to lung tumorigenesis through the adquisition of preneoplastic changes in lung epithelial cells. Inflammatory milieu increased the expression of PDCD1, TGFβ-1, MCP-1, LAG3, and Foxp3 and the presence of regulatory T cells within preneoplastic lesions. In addition concomitant chronic inflammation changed the K-ras mutational profile of the generated tumors from Q61R to G12D transition. In summary, these data identify early molecular mechanisms underlying lung carcinogenesis in an inflammatory context at different steps, providing a novel approach for the identification of drivers from preneoplastic to neoplastic lesions
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Project description:A novel RCAS-Cre-IRES-PyMT (RCI-PyMT) virus was designed to specifically knockout genes of interest in tumors generated in appropriate mutant mouse hosts. We used this tumor knockout, or TuKO, strategy to concisely ablate fgfr1 in PyMT induced mammary tumors in K19-tva/fgfr1loxP/loxP mice. The similarly injected control K19-tva mice developed mammary tumors exhibiting high metastasis penetration to lung, making this an ideal model for breast cancer metastasis. The fgfr1 TuKO tumors showed significantly decreased primary tumor growth, and most importantly, greatly reduced metastasis to lung. Our study suggests that FGFR1 signaling is a key pathway driving breast cancer lung metastasis and that targeting FGFR1 in breast cancer is an exciting approach to inhibit metastasis.
2017-06-12 | GSE85754 | GEO
Project description:Fibroblast growth factor receptor 1 (FGFR1) is a heavily N-glycosylated cell surface receptor tyrosine kinase, which in conjunction with fibroblast growth factors (FGFs) transmits signals through the plasma membrane. The balanced FGF/FGFR1 signaling is crucial for the development and homeostasis of human body and aberrant FGFR1 is often observed in various cancers. Besides predominant localization to the plasma membrane, FGFR1 was also detected inside cells, mainly in the nuclear lumen, where it modulates gene expression. However, the exact mechanism of FGFR1 nuclear transport is still unknown. In this study, we generated a glycosylation-free mutant of FGFR1, FGFR1.GF, and demonstrate that it is primarily localized to the nuclear envelope. We show that reintroduction of N-glycans in the D3 domain cannot redirect FGFR1 to the plasma membrane nor exclude the receptor from the nuclear envelope. Reestablishment of N-glycans of the D2 domain largely inhibits FGFR1 accumulation in the nuclear envelope, but receptor still accumulates inside the cell, mainly in the ER. Only the simultaneous presence of N-glycans of the D2 and D3 domains of FGFR1 supports the efficient transport of FGFR1 to the plasma membrane. Intracellular FGFR1.GF displays high level of autoactivation, suggesting the presence of nuclear FGFR1 signaling that is FGF independent. Using mass spectrometry and proximity ligation assay we identified novel binding partners of the nuclear envelope-localized FGFR1, providing insights into its cellular functions. Taken together, our data define N-glycosylation of FGFR1 as a significant regulator of FGFR1 kinase activity, and most importantly a switchable signal for FGFR1 trafficking between the nuclear envelope and the plasma membrane, which, due to the spatial restrictions, shapes the FGFR1 interactome and cellular function.
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Project description:Transcriptional changes in consequence of in vitro resistance development of FGFR1-driven DMS114 lung cancer cells against the multikinase inhibitor ponatinib
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Project description:RNA-seq data characterising neuroendocrine (NE) and non-NE cells, cultured on plastic or Matrigel, extracted from small cell lung cancer circulating tumour cell derived explants.
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