DrugMap: A quantitative pan-cancer analysis of cysteine ligandability (RNA-Seq)
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PROVIDER: PRJNA1079745 | ENA |
REPOSITORIES: ENA
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Project description:DrugMap: A quantitative pan-cancer analysis of cysteine ligandability
| PRJNA1079738 | ENA
Project description:DrugMap: A quantitative pan-cancer analysis of cysteine ligandability (ChIP-Seq)
| PRJNA1079741 | ENA
Project description:Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors of a wide-range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed DrugMap, an atlas of cysteine ligandability compiled across 416 cancer cell lines. We unexpectedly find that cysteine ligandability varies across cancer cell lines, and we attribute this to differences in cellular redox states, protein conformational changes, and genetic mutations. Leveraging these findings, we identify actionable cysteines in NFκB1 and SOX10 and develop corresponding covalent ligands that block the activity of these transcription factors. We demonstrate that the NFkB1 probe blocks DNA binding, whereas the SOX10 ligand increases SOX10-SOX10 interactions and disrupts melanoma transcriptional signaling. Our findings reveal heterogeneity in cysteine ligandability across cancers, pinpoint cell-intrinsic features driving cysteine targeting,and illustrate the use of covalent probes to disrupt oncogenic transcription factor activity
2024-04-23 | PXD047840 | Pride
Project description:SOX10 is a lineage-restricted transcription factor important for melanoma proliferation and survival. Our data demonstrate that SOX10 genetic depletion by CRISPR/Cas9 significantly impaired melanoma proliferation. We chose 7 different melanoma, all of which exhibited growth dependency on SOX10 with different levels. To define the SOX10 transcriptional signature shared with different SOX10-dependent melanoma, we performed bulk RNA-seq on 7 melanoma transfected with siSOX10 or siControl. Each melanoma cell line was plated and transfected with each siRNA to deplete SOX10 protein expression. After 72 hrs, cells were lysed with Buffer TCL(QIAGEN) supplemented with 2-ME and stored at -80C until use. Libraries from each cell line were made with the modified Smart-seq2 protocol. Each replicate was uniquely barcoded and all the samples were pooled for sequencing. (2) We developed a chemical probe (SH-0029) that covalently engages SOX10. To examine the effect of SH-0029 on SOX10 target genes, SOX10-dependent SKMEL5 melanoma were plated and treated with SH-0029, SH-0105 (a control probe), or DMSO(vehicle) for 48h. Total RNA was extracted with NucleoSpin RNA extraction kit (MACHEREY-NAGEL) and mRNA was subsequently purified with poly dT-attached magnetic beads. We found that downregulated genes induced by SH-0029 treatment strongly overlapped with those by SOX10 genetic depletion, suggesting that SOX10 covalent ligand controls SOX10 transcriptional network.
2024-04-24 | GSE256466 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-24 | GSE256467 | GEO
Project description:Pan-cancer circulating tumor DNA detection in over 10,000 real-world Chinese patients
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Project description:SOX10 plays important roles in development of neural crest lineages and melanocyte lineages. SOX10 binding sites on chromatin have been characterized in glial lineages, but fewer focused on melanoma. To examine chromatin occupancy of SOX10 and chromatin landscape in melanoma, we performed ChIP-seq analysis of SOX10 and H3K27ac in SOX10-dependent melanoma SKMEL5. We confirmed SOX10 binding in genes previously reported as direct targets of SOX10, including ERBB3 and IL16. Importantly, SOX10 chemical probe (SH-0029) treatment abrogated the expression of these genes, suggesting that pharmacological perturbation of SOX10 modifies SOX10 transcriptional network and downregulates SOX10 target genes.
2024-04-24 | GSE256464 | GEO
Project description:Metabolic reprogramming is a hallmark of human cancer and cancer-specific metabolism provide opportunities for cancer diagnosis, prognosis, and treatment. However, how metabolic pathways affect the initiation and progression of colorectal cancer remain largely unknown. Here, we showed cysteine is highly enriched in colorectal tumors compared with adjacent non-tumor tissues to promote tumorigenesis of CRC. Both cystine and cysteine imports are essential to maintain intracellular cysteine level and promote tumor growth and survival. Transporter genes of cystine and cysteine are all upregulated in colorectal cancer by tumor microenvironment induced ROS through transcription factor ATF4. Glutathione synthetase GSS is upregulated and increases cysteine to reduced glutathione flux to support tumor growth and survival in colorectal cancer. Depletion of cystine and cysteine by a recombinant cyst(e)inase effectively reduced the growth of colorectal tumors. Moreover, scavenging cystine and cysteine induces autophagy of colorectal cancer cells through mTOR-ULK signaling axis. With this study, we demonstrate that cysteine metabolism is a key signature of CRC metabolic reprogramming and targeting cysteine metabolism might be an effective approach to treat colon cancer.
2023-01-21 | GSE223118 | GEO
Project description:Metabolic reprogramming is a hallmark of human cancer and cancer-specific metabolism provide opportunities for cancer diagnosis, prognosis, and treatment. However, how metabolic pathways affect the initiation and progression of colorectal cancer remain largely unknown. Here, we showed cysteine is highly enriched in colorectal tumors compared with adjacent non-tumor tissues to promote tumorigenesis of CRC. Both cystine and cysteine imports are essential to maintain intracellular cysteine level and promote tumor growth and survival. Transporter genes of cystine and cysteine are all upregulated in colorectal cancer by tumor microenvironment induced ROS through transcription factor ATF4. Glutathione synthetase GSS is upregulated and increases cysteine to reduced glutathione flux to support tumor growth and survival in colorectal cancer. Depletion of cystine and cysteine by a recombinant cyst(e)inase effectively reduced the growth of colorectal tumors. Moreover, scavenging cystine and cysteine induces autophagy of colorectal cancer cells through mTOR-ULK signaling axis. With this study, we demonstrate that cysteine metabolism is a key signature of CRC metabolic reprogramming and targeting cysteine metabolism might be an effective approach to treat colon cancer.
2023-01-21 | GSE223119 | GEO
Project description:The following consists of an RNA-Seq cohort comprised of samples from patients diagnosed with various tumor types across the pan-cancer spectrum. Collected at diagnosis, these samples serve as a resource for tumor classification using machine learning classifiers. Process count tables are provided. This cohort can assist researchers in exploring molecular signatures and facilitate accurate classification across diverse malignancies.
2024-06-30 | E-MTAB-14038 | biostudies-arrayexpress