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Transcriptional heterogeneity among xenograft tumors derived from subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

ABSTRACT: Intratumoral heterogeneity has been described for various tumor types and models of human cancer, and can have profound effects on tumor progression and drug resistance. This study describes transcriptional heterogeneity among subclonal populations (SCPs) derived from a single triple-negative breast cancer cell line.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184541 | GEO | 2022/01/12

REPOSITORIES: GEO

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Transcriptional heterogeneity among subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

Project description:Intratumoral heterogeneity has been described for various tumor types and models of human cancer, and can have profound effects on tumor progression and drug resistance. This study describes transcriptional heterogeneity among subclonal populations (SCPs) derived from a single triple-negative breast cancer cell line.

2022-01-12 | GSE184540 | GEO

Transcriptional heterogeneity among MDA-MBA-468 triple-negative breast cancer cells

2022-01-12 | GSE184542 | GEO

Transcriptional heterogeneity among subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

Project description:Transcriptional heterogeneity among subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

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Transcriptional heterogeneity among xenograft tumors derived from subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

Project description:Transcriptional heterogeneity among xenograft tumors derived from subclonal populations of MDA-MBA-468 triple-negative breast cancer cells

| PRJNA765011 | ENA

Lipid remodeling in response to methionine stress in MDA-MBA-468 triple-negative breast cancer cells.

Project description:Methionine (Met) is an essential amino acid and critical precursor to the cellular methyl donor S-adenosylmethionine. Unlike nontransformed cells, cancer cells have a unique metabolic requirement for Met and are unable to proliferate in growth media where Met is replaced with its metabolic precursor, homocysteine. This metabolic vulnerability is common among cancer cells regardless of tissue origin and is known as "methionine dependence", "methionine stress sensitivity", or the Hoffman effect. The response of lipids to Met stress, however, is not well-understood. Using mass spectroscopy, label-free vibrational microscopy, and next-generation sequencing, we characterize the response of lipids to Met stress in the triple-negative breast cancer cell line MDA-MB-468 and its Met stress insensitive derivative, MDA-MB-468res-R8. Lipidome analysis identified an immediate, global decrease in lipid abundances with the exception of triglycerides and an increase in lipid droplets in response to Met stress specifically in MDA-MB-468 cells. Furthermore, specific gene expression changes were observed as a secondary response to Met stress in MDA-MB-468, resulting in a downregulation of fatty acid metabolic genes and an upregulation of genes in the unfolded protein response pathway. We conclude that the extensive changes in lipid abundance during Met stress is a direct consequence of the modified metabolic profile previously described in Met stress-sensitive cells. The changes in lipid abundance likely results in changes in membrane composition inducing the unfolded protein response we observe.

| S-EPMC8042402 | biostudies-literature

Proteomic analysis to examine the functional consequences of intratumor heterogeneity

Project description:To examine the functional consequences of intratumor heterogeneity, subclonal populations (SCPs) were derived from the MDA-MB-468 triple-negative breast cancer cell line. Characterization of these SCPs revealed considerable variation in SCP tumor forming capacity with SCP #32 (SCP32) having an exceptional high tumor forming capacity. To investigate the proteomic differences between tumors of SCP32 and other SCPs, in TMT1, isobaric tandem mass tag (TMT) labeling combined with LC-MS/MS (TMT-MS) was performed on tumors of SCP03, SCP29 and SCP32 (n = 3 each) collected at 2 months post transplantation. In TMT2, isobaric tandem mass tag (TMT) labeling combined with LC-MS/MS (TMT-MS) was performed on tumors of the parental MDA-MB-468 cell line (n = 2), and both barcoded and non-barcoded versions SCP29 and SCP32 (two each) collected at 2 months post transplantation.

2022-02-16 | PXD022325 | Pride

Transcriptional heterogeneity of MDA-MBA-468 triple-negative breast cancer cells

Project description:Transcriptional heterogeneity of MDA-MBA-468 triple-negative breast cancer cells

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Transcriptional heterogeneity among MDA-MBA-468 triple-negative breast cancer cells

Project description:Transcriptional heterogeneity among MDA-MBA-468 triple-negative breast cancer cells

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Transcriptional heterogeneity of MDA-MBA-468 triple-negative breast cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-01-12 | GSE184543 | GEO

Genomic and epigenomic architecture of hepatocellular carcinoma

Project description:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Understanding of the intratumoral heterogeneity of HCC is instructive for developing personalized therapy and molecular biomarkers. We applied whole exome sequencing to a total of 63 samples from 11 patients to resolve the genetic architecture and subclonal diversification. Notably, spatial genomic diversity was found in all 11 HCC cases, with 33% of the driver mutations being heterogeneous. Temporal dissection of mutational signatures suggested that exogenous and endogenous factors have different contributions in shaping the mutational spectrum during the development of HCC. Moreover, we observed extensive intratumoral epigenetic heterogeneity in HCC, and showed that integrative analysis of both genetic and epigenetic phylogenies could generate more robust resolution of clonal architecture than single profiling approach. Our results also demonstrated prominent epigenetic subclonal diversification even in a stable HCC genome. Together, these findings highlight the widespread intratumoral heterogeneity at both genomic and epigenomic levels in HCC, and provide important molecular foundation for better understanding of the biology and pathogenesis of this malignancy.

2017-03-03 | GSE83691 | GEO

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