Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA284760 | ENA |
REPOSITORIES: ENA
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Project description:CEACAM family proteins have been extensively studied as cell adhesion molecules, yet the biological and clinical significance of CEACAM6 remains relatively unexplored. Our research identifies a significant increase in CEACAM6 expression in lung adenocarcinoma, particularly correlating with EGFR mutation status. In EGFR-mutated lung cancer cells, CEACAM6 knockdown induced apoptosis and reduced p-ERK1/2 signaling downstream of EGFR. Treatment with EGFR-tyrosine kinase inhibitors (TKIs) decreased CEACAM6 levels, leading to TKI-resistant lung cancer cells that exhibited reduced p-ERK1/2 and increased epithelial-mesenchymal transition (EMT) characteristics. Co-immunoprecipitation assays revealed an interaction between CEACAM6 and EGFR. Although CEACAM6 expression was lost in EGFR-TKI resistant cells, its re-expression stabilized EGFR and increased sensitivity to EGFR-TKIs. TGF-? treatment, which induced EMT, also decreased CEACAM6 expression and improved EGFR-TKI resistance. Further analysis showed that EGFR-TKI resistant lung cancer cells had lower H3K27ac epigenetic modification levels at the CEACAM6 locus than EGFR-TKI sensitive cells. Treatment with HDAC1/2 inhibitors in EGFR-TKI sensitive cells reduced CEACAM6 expression, induced EMT and TGF-?-ligand/receptor gene expression, and enhanced EGFR-TKI resistance. These data highlight the crucial role of CEACAM6 in maintaining oncogenic EGFR signaling and its regulation by cytokine stimulation and epigenetic modification, influencing EGFR-TKI sensitivity. Our findings underscore CEACAM6's potential as a valuable biomarker in EGFR-driven lung adenocarcinoma and its intricate involvement in EGFR-related pathways.
2025-04-30 | GSE289000 | GEO
Project description:Whole exome sequencing was performed on set of 48 DNA samples obtained from 16 EGFR mutated NSCLC patients whose tumors progressed following EGFR-TKI treatment. The DNA samples included baseline biopsy, rebiopsy and blood from the same patient. By comparing the variants in rebiopsy tumors and baseline tumors we aim to understand the genomic alterations responsible for the development of EGFR-TKI resistance in NSCLC patients.
2022-02-11 | E-MTAB-11404 | biostudies-arrayexpress
Project description:Differential mRNA expression analysis of EGFR-TKI-sensitive cells vs. EGFR-TKI-resistant cells
| PRJNA721680 | ENA
Project description:A Cartes d'Identite des Tumeurs (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net ) : 165 lung adenocarcinomas without prior chemotherapy, hybridized on Illumina SNP HumanCNV370 and Affymetrix HGU133Plus2 arrays. Project leader : Prof. Pierre FOURET (pierre.fouret@igr.fr). Note: Bronchiolo-alveolarComponent : a non invasive tumor component shown in well differentiated tumor cells. EGFR Gene Mutation Status: Gene mutation status of epidermal growth factor receptor (erythroblastic leukemia viral (v; -erb-b) ; oncogene homolog, avian) ; HGNC:3236 ; Approved Symbol:EGFR; Chromosome:7p12 ; UniProt ; ID:P00533 ; OMIMID:131550 ; EntrezGeneID:1956 ; ; RefSeq:NM_201283 ; M=mutated ; WT=non mutated=wild type. KRAS Gene Mutation Status: Gene mutation status of v-Ki-ras2 Kirsten rat ; sarcoma viral oncogene homolog ; HGNC:6407 ; Approved Symbol:KRAS ; Chromosome:12p12.1 ; UniProtID:P01116; OMIM ID:190070 ; EntrezGeneID:3845 ; ;RefSeq:NM_033360 ; M=yes=mutated ; WT=non mutated.
2012-10-19 | E-MTAB-923 | biostudies-arrayexpress
Project description:Lung adenocarcinoma cells harboring epidermal growth factor receptor (EGFR) mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs). Prolonged cancer treatment will induce the development of acquired resistance to EGFR TKI. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, we generate EGFR-TKI-resistant HCC827-8-1 cells to be analyzed by microarray with their parental HCC827cells. gefitinib resistant HCC827-8-1 cells with three replications; gefitinib-sensitive HCC827 cells with three replications
2016-08-23 | E-GEOD-74575 | biostudies-arrayexpress
Project description:Contains WES and RNA-seq for the 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC.
| EGAD00001010272 | EGA
Project description:Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance remains unknown. We determined gene expression profiling in EGFR-TKI-resistant cells using RNA-seq analysis
2021-04-18 | GSE172002 | GEO
Project description:Treatment of lung adenocarcinomas (LUAD) that exhibit activated epidermal growth factor receptor (EGFR) with EGFR tyrosine kinase inhibitors (TKI) has limited efficacy. Assessment of the impact of EGFR TKI on the LUAD surfaceome remodeling revealed potential therapeutic targets. We identified placental type alkaline phosphatase (ALPP) which has restricted expression in normal tissues, among upregulated surface proteins following EGFR TKI treatment of both TKI sensitive as well as resistant cells. Upregulation of ALPP with EGFR TKI resulted from activation of FoxO3a. The combination of EGFR TKI plus ALPP antibody conjugated with monomethylauristatin F enhanced tumor killing in osimertinib-sensitive and osimertinib-resistant LUAD models compared to either treatment alone. Our findings point to surfaceome remodeling induced with an established cancer therapy as a means for the development of more effective combination therapies.
2025-10-09 | PXD069074 | Pride
Project description:Intrinsic and acquired resistance represent major obstacles to optimize outcomes in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeted therapy in lung adenocarcinoma (LUAD). Hence, a deeper understanding of EGFR-TKI resistance mechanisms in LUAD will potentially assist in formulating strategies to delay or overcome such resistance. Herein, it was observed that trefoil factor 3 (TFF3) is a crucial mediator of the LUAD EGFR-TKI response. TFF3 conferred intrinsic resistance to EGFR inhibition in LUAD by promotion of EGFR activation. TFF3 expression was also increased in acquired EGFR-TKI resistant LUAD, accompanied by reduced EGFR activation. YAP, a key mediator of the Hippo signaling, was positively regulated by TFF3 by post-transcriptional mechanisms and was responsible for acquired EGFR-TKI resistance mediated by TFF3. Inhibition of TFF3 by a small molecule inhibitor not only enhanced EGFR-TKI sensitivity in LUAD cells but also restored the sensitivity of acquired EGFR-TKI resistant LUAD cells to EGFR-TKIs in vitro and in vivo. These findings demonstrate a pivotal function of TFF3 in mediating EGFR-TKI resistance in LUAD and may offer a potential therapeutic mechanism for delaying or overcoming resistance to EGFR-TKIs.
2025-10-31 | GSE276990 | GEO
Project description:Epidermal growth factor receptor (EGFR) harboring active mutations, Del19 and L858R, are most common oncogenic mutations in in non-small cell lung cancer (NSCLC) patients. The preferred treatment at first line is tyrosine kinase inhibitor (TKI) administration while the TKI-resistance usually develops because of acquiring the secondary EGFR T790M mutant. Protein-protein interactions (PPIs) constitute the signaling scaffold and thus aberrant PPIs ascribed to mutations often results in dysregulations of downstream signaling cascades. Affinity purification coupled mass spectrometry (AP-MS) was utilized to characterize the EGFR PPIs in four NSCLC cells which carry different EGFR subtypes representing as TKI-sensitive and -resistant models in this study. The EGFR interactomes of TKI-resistant NSCLC cells presented higher diversity of subcellular distribution as well as the hyperactive EGFR trafficking. Furthermore, gefitinib perturbation activated autophagy-mediated EGFR degradation in TKI-resistant NSCLC models and inhibiting autophagy process indeed reduced the TKI-resistance against gefitinib as cytotoxicity was significantly improved. Alternatively, gefitinib induced EGFR translocation toward cell periphery through Rab7 ubiquitination in TKI-sensitive models which may confer TKIs more chance to suppress EGFR activity. In brief, acquired T790M EGFR mutation rewired the EGFR inherent interactomes and thus guided EGFR moving toward distinct trafficking routes, EGFR recycling or autophagy-mediated degradation, in response to TKI insult in TKI-sensitive and -resistant NSCLC cells. These finding suggest that manipulation or combined autophagy inhibition may provide us a novel therapeutic strategy to manage TKI-resistance and tumor relapse in NSCLC.
2023-05-31 | PXD034228 | JPOST Repository