Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

841fd1a1-3b4c-4aba-9193-0eb3a987236c - samples

ABSTRACT: Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from both chemotherapies and targeted agents. It is increasingly appreciated that the DTP state is an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer xenograft models to identify and characterize the cancer cells capable of generating DTPs in response to standard-of-care chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model in which all cancer cells, and not a small subpopulation, possess an equipotent capacity to enter the DTP state. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides new insights into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target diapause-like DTPs.

PROVIDER: EGAD00001006849 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Colorectal cancer cells possess an equipotent capacity to enter a reversible diapause-like state to survive chemotherapy

Project description:Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from chemotherapies and targeted agents. It is increasingly appreciated that DTPs are an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target DTPs.

2021-01-07 | GSE145356 | GEO

Colorectal cancer cells possess an equipotent capacity to enter a developmental pausing-like state to survive chemotherapy

Project description:Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from both chemotherapies and targeted agents. It is increasingly appreciated that the DTP state is an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer xenograft models to identify and characterize the cancer cells capable of generating DTPs in response to standard-of-care chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model in which all cancer cells, and not a small subpopulation, possess an equipotent capacity to enter the DTP state. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides new insights into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target diapause-like DTPs.

| EGAS00001004773 | EGA

Regulation of chemosensitivity in pancreatic cancer cells

Project description:We performed RNA-seq to investigate gene expression changes in pancreatic cancer cells following chemotherapeutic drug treatment. We identify a reversible senescence state among the drug-tolerant persister cells.

2022-08-22 | GSE189764 | GEO

Cycling cancer persisters arise from lineages with distinct transcriptional and metabolic programs

Project description:Non-genetic mechanisms have recently emerged as important drivers of therapy failure in cancer, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment. While most cancer persisters, like their bacterial counterparts, remain arrested in the presence of drug, a rare subset of cancer persisters can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to simultaneously resist therapy and maintain proliferative capacity in the presence of drug. To address this, we developed Watermelon, a new high-complexity expressed barcode lentiviral library for simultaneous tracing each cell's clonal origin, proliferative state, and transcriptional state, and used it to study this rare, transiently-resistant, proliferative persister population and identify what distinguishes it from non-cycling persisters. Analysis of Watermelon-transduced cancer cell lines demonstrated that cycling and non-cycling persisters arise from different pre-existing cell lineages with distinct transcriptional and metabolic programs. The proliferative capacity of persisters is associated with an upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation in specific subpopulations of tumor cells.

2020-05-21 | GSE150949 | GEO

Colorectal cancer cells possess an equipotent capacity to enter a reversible diapause-like state to survive chemotherapy

Project description:Colorectal cancer cells possess an equipotent capacity to enter a reversible diapause-like state to survive chemotherapy

| PRJNA606811 | ENA

Genome-wide analysis of DNA methylation in drug-tolerant cancer cell subpopulations

Project description:Cancer relapse after curative treatment is thought to originate from drug-tolerant and invisible cancer cell subpopulations. Using cancer cell colonies emerging in the presence of drugs (drug-tolerant colonies, DTCs), we found that the drug-tolerant properties of DTCs are lost through a reversible mechanism. To examine whether epigenetic regulation is responsible for the phenotypic changes in DTCs, we performed a genome-wide analysis for relative CpG methylation between the DTCs and untreated colonies derived from MKN45 by NimbleGen Human Meth 385K Prom Plus CpG Arrays. Global changes in the methylation levels were evident in a chromosomal location-dependent manner. The methylation status of the upstream regions of the transcription start sites of the pluripotency-inducing genes showed good agreement with the qRT-PCR data. These results suggest that reversible drug-tolerant properties in DTCs are epigenetically regulated and associated with transcriptional regulation, including pluripotency-inducing factors. Comparison of untreated colonies v.s. DTCs derived from MKN45 cells.

2015-05-26 | E-GEOD-69203 | biostudies-arrayexpress

Drug-tolerant cancer cell persisters survive lethal exposures by silencing transposable elements [ChIP-Seq]

Project description:Establishing and maintaining phenotypic heterogeneity within cell and organismal populations is an evolutionarily conserved strategy that ensures survival of the population following stressful exposures. We previously identified a transient, reversible, drug-tolerant cancer cell subpopulation that survives otherwise lethal drug exposures. Here we show that these drug-tolerant persisters (DTPs) assume a highly heterochromatic state, which requires factors that modify or bind trimethylated H3 lysine 9 (H3K9me3). The increased H3K9me3 in DTPs is largely restricted to evolutionarily young Long Interspersed Repeat elements (LINEs). This transcriptionally repressive state, which decreases the expression of these retrotransposable elements, is critical for DTP survival, and disruption of this heterochromatic state results in re-expression of LINE elements and ablation of this subpopulation. Together, these findings establish a role for epigenetic silencing of transposable elements as a population survival strategy to maintain genomic integrity in subpopulations of cancer cells during lethal drug exposures.

2017-07-03 | GSE74179 | GEO

Repression of stress-induced LINE-1 expression protects cancer cell populations from lethal drug-exposures [ATAC-Seq]

2017-07-03 | GSE73874 | GEO

mTOR activity paces human blastocyst stage developmental progression (data set 2)

Project description:Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway1. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies.

2024-09-26 | PXD036258 | Pride

mTOR activity paces human blastocyst stage developmental progression (data set 1)

2024-08-06 | PXD029513 | Pride