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Transcriptional heterogeneity among 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: GSE184540 | GEO | 2022/01/12

REPOSITORIES: GEO

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Transcriptional heterogeneity among xenograft tumors derived from 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.

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

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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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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.

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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

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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.

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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.

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

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