Oxidative phosphorylation promotes primary melanoma invasion
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA602818 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10956566_1.fastq.gz | Fastqsanger.gz | |||
| SRR10956566_2.fastq.gz | Fastqsanger.gz | |||
| SRR10956567_1.fastq.gz | Fastqsanger.gz | |||
| SRR10956567_2.fastq.gz | Fastqsanger.gz | |||
| SRR10956568_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Dermal invasion is a hallmark of malignant melanoma. The molecular alterations driving the progression of primary melanoma to metastatic disease have been studied extensively, whereas the early progression of non-invasive primary melanoma to an invasive state is not well understood. To elucidate the mechanisms underlying the transition from radial to vertical growth, the first step in melanoma invasion, we developed a zebrafish melanoma model in which constitutive activation of ribosomal protein S6 kinase 1 (RSK1) drives tumor invasion. Transcriptomic analysis of RSK1-activated tumors identified metabolic changes, including upregulation of genes associated with oxidative phosphorylation. Vertical growth phase human melanoma cells show higher oxygen consumption and preferential utilization of glutamine compared to radial growth phase melanoma cells. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1a has been proposed as a master regulator of tumor oxidative phosphorylation. In human primary melanoma specimens we show that PGC1a protein expression is positively associated with increased tumor thickness and expression of the proliferative marker Ki-67 and the reactive oxygen species (ROS) scavenger SCARA3. PGC1a depletion modulates cellular processes associated with primary melanoma growth and invasion, including oxidative stress. Our results support a role for PGC1a in mediating glutamine-driven OXPHOS to facilitate the invasive growth of primary melanoma.
2020-01-24 | GSE144117 | GEO
Project description:Dermal invasion is a hallmark of malignant melanoma. Although the molecular alterations that drive the progression of primary melanoma to metastatic disease have been studied extensively, the early progression of noninvasive primary melanoma to an invasive state is poorly understood. To elucidate the mechanisms underlying the transition from radial to vertical growth, the first step in melanoma invasion, we developed a zebrafish melanoma model in which constitutive activation of ribosomal protein S6 kinase A1 drives tumor invasion. Transcriptomic analysis of ribosomal protein S6 kinase A1-activated tumors identified metabolic changes, including up-regulation of genes associated with oxidative phosphorylation. Vertical growth phase human melanoma cells show higher oxygen consumption and preferential utilization of glutamine compared to radial growth phase melanoma cells. Peroxisome proliferator activated receptor γ coactivator (PGC)-1α, has been proposed as a master regulator of tumor oxidative phosphorylation. In human primary melanoma specimens, PGC1α protein expression was found to be positively associated with increased tumor thickness and expression of the proliferative marker Ki-67 and the reactive oxygen species scavenger receptor class A member 3. PGC1α depletion modulated cellular processes associated with primary melanoma growth and invasion, including oxidative stress. These results support a role for PGC1α in mediating glutamine-driven oxidative phosphorylation to facilitate the invasive growth of primary melanoma.
| S-EPMC7237828 | biostudies-literature
Project description:Oxidative stress has been shown to limit metastasis of numerous cancer types including melanoma. A specialized group of 25 proteins containing the 21st amino acid, selenocysteine, plays a central role in oxidative stress resistance, which is a key driver of metastasis. A single selenocysteine tRNA methylation, Um34, is required for the translation of several stress-related selenoproteins in a selenium-dependent manner. Herein, we characterize FTSJ1 as the Um34 methyltransferase and show that its activity is required for the Sec tRNA (tRNASec) Um34 modification. Loss of Um34 affects translation of a subset of selenoproteins and increases melanoma cell sensitivity to oxidative stress while increased Um34 levels promote oxidative stress resistance. Loss of FTSJ1 does not affect primary melanoma tumor growth but abolishes metastatic spread in vivo. Overexpression of FTSJ1 specifically increases melanoma metastasis in vivo. Our work establishes FTSJ1 as the Um34 methyltransfearse and tRNASec Um34 modification as a central regulator of oxidative stress resistance during melanoma metastasis.
2024-09-03 | GSE270971 | GEO
Project description:Local invasion is a critical early step in metastatic cancer. This study investigated the invasion mechanisms of primary (IGR39) and metastatic (IGR37) melanoma cells at the single-cell level using single-probe single-cell mass spectrometry (SCMS). We detected 166 of 228 metabolites in IGR39 and 168 of 172 in IGR37.
2025-08-12 | MSV000098805 | GNPS
Project description:Background: Melanoma brain metastases (MBM) continues to be a significant clinical problem with limited treatment options. Highly invasive melanoma cells migrate along the vasculature and perivascular cells may contribute to residual disease and recurrence. PTEN loss and hyperactivation of AKT occur in MBM; however, a role for PTEN/AKT in perivascular invasion has not been described. Methods: We used in vivo intracranial injections of murine melanoma and bulk RNA sequencing of melanoma cells co-cultured with brain endothelial cells (brECs) to investigate brain colonization and perivascular invasion. Results: We found that PTEN-null melanoma cells were highly efficient at colonizing the perivascular niche relative to PTEN-expressing counterparts. PTEN re-expression (PTEN-RE) in melanoma significantly reduced brain colonization and migration along the vasculature. We hypothesized this phenotype was mediated through vascular-induced TGFβ secretion, which drives AKT phosphorylation. Disabling TGFβ signaling in melanoma cells reduced colonization and perivascular invasion; however, introduction of constitutively-active myristolated-AKT (myrAKT) restored overall tumor size but not perivascular invasion. Conclusions: PTEN loss facilitates perivascular brain colonization and invasion of melanoma. TGFβ-AKT signaling partially contributes to this phenotype, but further studies are needed to determine the complementary mechanisms that enable melanoma cells to both survive and spread along the brain vasculature.
2023-12-26 | GSE247232 | GEO
Project description:Oxidative stress has been shown to limit metastasis of numerous cancer types including melanoma. A specialized group of 25 proteins containing the 21st amino acid, selenocysteine, plays a central role in oxidative stress resistance, which is a key driver of metastasis. A single selenocysteine tRNA methylation, Um34, is required for the translation of several stress-related selenoproteins in a selenium-dependent manner. Herein, we characterize FTSJ1 as the Um34 methyltransferase and show that its activity is required for the Sec tRNA (tRNASec) Um34 modification. Loss of Um34 affects translation of a subset of selenoproteins and increases melanoma cell sensitivity to oxidative stress while increased Um34 levels promote oxidative stress resistance. Loss of FTSJ1 does not affect primary melanoma tumor growth but abolishes metastatic spread in vivo. Overexpression of FTSJ1 specifically increases melanoma metastasis in vivo. Our work establishes FTSJ1 as the Um34 methyltransfearse and tRNASec Um34 modification as a central regulator of oxidative stress resistance during melanoma metastasis.
2024-09-03 | GSE270976 | GEO
Project description:CircGLIS3 promotes high-grade glioma invasion via modulating Ezrin phosphorylation
| PRJNA698359 | ENA
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165859 | GEO
Project description:Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
| PRJNA880299 | ENA
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
2021-09-22 | GSE165926 | GEO