Plakophilin 1 enhances MYC expression to promote squamous cell lung cancer
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ABSTRACT:
PROVIDER: PRJNA417944 | ENA |
REPOSITORIES: ENA
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Project description:Plakophilin 1 (PKP1) is a component of desmosomes. Although desmosome function loss has been associated with increased cell migration and pro-oncogenic activity, we previously observed PKP1 overexpression in squamous cell lung cancer (SqCLC). We developed in vitro and in vivo functional models of PKP1 gain/loss in SqCLC to explore this paradox. Greater cell dissemination but reduced cell proliferation was observed in CRISPR-Cas9 PKP1-knockout clones. PKP1 expression promoted cell proliferation, cell survival, and in vivo xenograft engraftment, and these pro-oncogenic activities were mediated by the functional relationship of PKP1 with MYC. PKP1 bound to the 5’UTR of MYC mRNA, enhancing MYC translation, and MYC bound directly to the PKP1 promoter, enhancing PKP1 transcription. We propose PKP1 as a novel oncogene in SqCLC and a post-transcriptional regulator of MYC. PKP1 may be a valuable diagnostic biomarker and potential therapeutic target for SqCLC. Importantly, PKP1 inhibition may indirectly target MYC, a primary anti-cancer target.
2020-05-10 | GSE106770 | GEO
Project description:Lung squamous cell carcinoma (LSCC) is a considerable global health burden, with an incidence of over 600,000 cases per year. Treatment options are limited, and patient 5-year survival rate is less than 5%. The ubiquitin specific protease 28 (USP28) has been implicated in tumorigenesis through its stabilization of the oncoprotein c-MYC. Here, we show that genetic inactivation of USP28 induced regression of established murine LSCC lung tumors. We developed small molecule USP28 inhibitors that inhibit USP28 activity in the low nanomole range. While displaying considerable activity against the closest homologue USP25, these inhibitors showed a high degree of selectivity over other deubiquitinases. USP28 inhibitor treatment resulted in a dramatic decrease in c-Myc proteins levels and consequently induced substantial regression of autochthonous murine LSCC tumors and human LSCC xenografts, thereby phenocopying the effect observed by genetic deletion. Thus, USP28 may represent a promising therapeutic target for the treatment of squamous cell lung carcinoma.
2024-07-30 | PXD023339 | Pride
Project description:Quantitative proteomic profiling the lung squamous carcinoma cells
2016-07-14 | MSV000079911 | MassIVE
Project description:MYC is a master regulator of transcription in growing cells. Menin is an enigmatic protein that displays unique ability to either suppress or promote tumorigenesis in a context dependent manner. It's interesting to ask is there any relationship between MYC and menin.Here, we used RNA-seq to study global transcriptomic expression of MYC or MEN1 knockdown HT1080 cells to investigate whether there are any correlations between MYC- and menin- regulated gene expression. Besides, we performed ChIP-seq assays for MYC and Menin binding sequences to address whether Menin and MYC share some common binding sites on chromatin.
2017-06-09 | GSE86504 | GEO
Project description:Protein Co-expression Network-based Profiles Revealed from Laser-microdissected Cancerous Cells of Lung Squamous-Cell Carcinomas
2021-07-19 | PXD027381 | JPOST Repository
Project description:Lung squamous cell carcinoma (LUSC) is associated with high mortality and limited targeted therapies. USP13 is one of the most amplified genes in LUSC, and yet its role in lung cancer is largely unknown. Here, we establish a novel mouse model of LUSC by overexpressing USP13 in KrasG12D/+; Trp53flox/flox background (KPU). KPU model faithfully recapitulates the key pathohistological, molecular features, and cellular pathways of human LUSC. We found that USP13 altered lineage-determining factors such as NKX2-1 and SOX2 in club cells (CC10+) of the airway and reinforced the fate of club cells to squamous carcinoma development. We also showed a strong molecular association between USP13 and MYC, leading to the upregulation of squamous programs in murine and human lung cancer cells. Collectively, our data demonstrate USP13 as a molecular driver of lineage plasticity in club cells and provide mechanistic insight that may have potential implications for the treatment of NSCLC.
2024-01-02 | GSE244847 | GEO
Project description:To identify gene expression biomarkers associate with asbestos-related lung squamous cell carcinoma, we analyzed gene expression profiles for a total of 56 lung squamous cell carcinomas using 44K Illumina Gene Expression microarrays. Twenty-six cases had lung asbestos body counts above levels associated with urban dwelling (ARLC-SCC: asbestos-related lung cancer-squamous cell carcinoma) and 30 cases had no lung asbestos bodies (NARLC-SCC: non-asbestos related lung cancer- squamous cell carcinoma). Genes differentially expressed between ARLC-SCC and NARLC-SCC were identified on fold change and P-value, and then prioritised using gene ontology. Total RNA was obtained from fresh frozen lung tumour tissue and stratified by asbestos phenotype. Gene expression profiling was performed to identify differences in the gene profiles of asbestos-related and non-asbestos related lung squamous cell carcinomas.
2012-01-30 | E-GEOD-23822 | biostudies-arrayexpress
Project description:The differential diagnosis between head & neck squamous cell carcinomas and lung squamous cell carcinomas is often unresolved because the histologic appearance of these two tumor types is similar. In the development of a gene expression profile test (GEP-HN-LS) that distinguishes these 2 cancer types, a collection of poorly differentiated primary and metastatic tumor specimens were used. Here we describe 76 such tumor specimens that were used for validation of GEP-HN-LS. The specimens are either head & neck squamous cell carcinomas or lung squamous cell carcinomas. All tissue specimens were formalin fixed paraffin embedded specimens. Gene expression was profiled using Affymetrix GeneChip platform.
2013-03-10 | E-GEOD-44170 | biostudies-arrayexpress
Project description:We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells). Human lung squamous BEAS-2B cells were transduced for Control or SOX2 expression, and their transcriptomes compared using Affymetrix arrays.
2010-02-21 | E-GEOD-14883 | biostudies-arrayexpress
Project description:To investigate molecular changes occurring during lung adenocarcinoma to squamous carcinoma transformation.
2023-02-28 | GSE226068 | GEO