Dataset's files
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| GSE234472_RAW.tar | Raw | |||
| filelist.txt | Txt |
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Similar Datasets
Project description:We performed single cell RNA sequencing analysis from KRAS G12V mouse tumor nodules from different treatment.
2024-12-18 | GSE234471 | GEO
Project description:We performed bulk-RNA sequencing analysis from KRAS G12V mouse tumor nodules from different treatment.
2024-12-18 | GSE234470 | GEO
Project description:Targeted degradation of oncogenic KRAS G12V triggers antitumor immunity in lung cancer
| PRJNA981494 | ENA
Project description:Targeting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4'-trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD-L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG-CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD-L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor-infiltrating T-cell immunity and reduce the immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA-4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.
| S-EPMC11208742 | biostudies-literature
Project description:The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer. This SuperSeries is composed of the following subset Series:; GSE17643: Profiling of immortalized human lung epithelial cells following oncogenic KRAS expression and TBK1 suppression; GSE17671: Profiling of immortalized human lung epithelial cells following infection with oncogenic KRAS (G12V) Experiment Overall Design: Refer to individual Series
2009-10-31 | E-GEOD-17672 | biostudies-arrayexpress
Project description:The purpose of the dataset is to analyze expression of genes induced by KRAS; The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer. Experiment Overall Design: Profiling of KRAS activation (mutant), KRAS WT and control in AALE cells (Lundberg et al., Oncogene 2002;21:4577)
2009-10-31 | E-GEOD-17671 | biostudies-arrayexpress
Project description:Recent advances in molecular biology and the resultant identification of driver oncogenes have achieved major progress in precision medicine for non-small-cell lung cancer (NSCLC). v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in NSCLC, and targeting KRAS is considerably important. The recent discovery of covalent KRAS G12C inhibitors offers hope for improving the prognosis of NSCLC patients, but the development of combination therapies corresponding to tumor characteristics is still required given the vast heterogeneity of KRAS-mutated NSCLC. In this review, we summarize the current understanding of KRAS mutations regarding the involvement of malignant transformation and describe the preclinical and clinical evidence for targeting KRAS-mutated NSCLC. We also discuss the mechanisms of resistance to KRAS G12C inhibitors and possible combination treatment strategies to overcome this drug resistance.
| S-EPMC8656763 | biostudies-literature
Project description:The purpose of the dataset is to analyze expression of genes induced by KRAS The proto-oncogene KRAS is mutated in a wide array of human cancers, most of which are aggressive and respond poorly to standard therapies. Although the identification of specific oncogenes has led to the development of clinically effective, molecularly targeted therapies in some cases, KRAS has remained refractory to this approach. An alternative strategy for targeting KRAS is to identify gene products that, when suppressed or inhibited, result in cell death only in the presence of an oncogenic allele. Here we have used systematic RNA interference (RNAi) to detect synthetic lethal partners of oncogenic KRAS and found that the non-canonical IkB kinase, TBK1, was selectively essential in cells that harbor mutant KRAS. Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression. In these cells, TBK1 activated NF- B anti-apoptotic signals involving cREL and BCL-XL that were essential for survival, providing mechanistic insights into this synthetic lethal interaction. These observations identify TBK1 as a potential therapeutic target in KRAS mutant tumors and establish a general approach for the rational identification of co-dependent pathways in cancer.
2009-10-21 | GSE17671 | GEO
Project description:Lung cancer is the leading cause of cancer related deaths worldwide. The present study investigated the effects of naproxen (NSAID) on lung adenocarcinoma in spontaneous lung cancer mouse model. Six-week-old transgenic KrasG12V mice (n = 20; male + female) were fed modified AIN-76A diets containing naproxen (0/400 ppm) for 30 wk and euthanized at 36 wk of age. Lungs were evaluated for tumor incidence, multiplicity, and histopathological stage (adenoma and adenocarcinoma). Lung tumors were noticeable as early as 12 wk of age exclusively in the KrasG12V mice. By 36 wk age, 100% of KrasG12V mice on control diet developed lung tumors, mostly adenocarcinomas. KrasG12V mice fed control diet developed 19.8 ± 0.96 (Mean ± SEM) lung tumors (2.5 ± 0.3 adenoma, 17.3 ± 0.7 adenocarcinoma). Administration of naproxen (400 ppm) inhibited lung tumor multiplicity by ∼52% (9.4 ± 0.85; P < 0001) and adenocarcinoma by ∼64% (6.1 ± 0.6; P < 0001), compared with control-diet-fed mice. However, no significant difference was observed in the number of adenomas in either diet, suggesting that naproxen was more effective in inhibiting tumor progression to adenocarcinoma. Biomarker analysis showed significantly reduced inflammation (COX-2, IL-10), reduced tumor cell proliferation (PCNA, cyclin D1), and increased apoptosis (p21, caspase-3) in the lung tumors exposed to naproxen. Decreased serum levels of PGE2 and CXCR4 were observed in naproxen diet fed KrasG12V mice. Gene expression analysis of tumors revealed a significant increase in cytokine modulated genes (H2-Aa, H2-Ab1, Clu), which known to further modulate the cytokine signaling pathways. Overall, the results suggest a chemopreventive role of naproxen in inhibiting spontaneous lung adenocarcinoma formation in KrasG12V mice.
| S-EPMC8187931 | biostudies-literature
Project description:The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered "undruggable" due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-l- and all-d-amino acid biotinylated variants of oncogenic mutant KRas(G12V). The protein is synthesized using Fmoc-based solid-phase peptide synthesis and assembled using combined native chemical ligation and isonitrile-mediated activation strategies. We demonstrate that both KRas(G12V) enantiomers can successfully fold and bind nucleotide substrates and binding partners with observable enantiodiscrimination. By demonstrating the functional competency of a mirror-image form of KRas bound to its corresponding enantiomeric nucleotide triphosphate, this study sets the stage for further biochemical studies with this material. In particular, this protein will enable mirror-image yeast surface display experiments to identify all-d peptide ligands for oncogenic KRas, providing a useful tool in the search for new therapeutics against this challenging disease target.
| S-EPMC5606205 | biostudies-literature