Asymmetric cancer cell division regulated by AKT, Reactive Oxygen Species (ROS) high versus ROS low mRNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE30465 | GEO | 2011/07/15
SECONDARY ACCESSION(S): PRJNA143495
REPOSITORIES: GEO
Similar Datasets
Project description:Human tumors often contain slowly proliferating cancer cells that resist treatment but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating “G0-like” progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur. 3 replicates each of MCF7 Reactive Oxygen Species (ROS) high, HCT116 ROS high, MCF7 ROS low, and HCT116 ROS low.
2011-07-14 | E-GEOD-30465 | biostudies-arrayexpress
Project description:Our earlier study demonstrated that when CFSE-labeled LCMV-or Pichinde virus-immune spleen leukocytes were transferred into T cell-deficient hosts, the bona fide virus-specific memory cells underwent relatively limited cell division and were substantially diluted in frequency by other more extensively proliferating cells originating from that donor cell population. We questioned how the slowly dividing population, which contained bona fide memory cells, differed from the rapidly dividing cells, which contained “memory-like” cells. As a preliminary screen we performed a comparative genome-wide microarray analysis of genes expressed on sorted rapidly proliferating (CFSE-low) and slowly proliferating (CFSE-high) CD8 cell populations Keywords: Division profile comparison
2008-07-25 | GSE8584 | GEO
Project description:Our earlier study demonstrated that when CFSE-labeled LCMV-or Pichinde virus-immune spleen leukocytes were transferred into T cell-deficient hosts, the bona fide virus-specific memory cells underwent relatively limited cell division and were substantially diluted in frequency by other more extensively proliferating cells originating from that donor cell population. We questioned how the slowly dividing population, which contained bona fide memory cells, differed from the rapidly dividing cells, which contained âmemory-likeâ cells. As a preliminary screen we performed a comparative genome-wide microarray analysis of genes expressed on sorted rapidly proliferating (CFSE-low) and slowly proliferating (CFSE-high) CD8 cell populations Experiment Overall Design: 2x10^7 CFSE-labeled, Ly5.1+, LCMV-Immune splenocytes were adoptively transferred into congenic T cell ko hosts. Splenocytes were harvested 12 days post-transfer and stained with anti-CD8 Ab, anti-Ly5.1 Ab and 7AAD. 7AAD negative cells were gated, and CFSE-low (> eight divisions) and CFSE-high (0-6 divisions) cells were sorted by flow cytometry using a FACStarPLUS sorter (BD Bioscience, Mountain View, CA). Total RNA was extracted from both CFSE-low and CFSE-high CD8+Ly5.1+ donor populations to compare rapidly vs. slowly dividing CD8 T cells during acute homeostatic proliferation via Affymetrix gene analysis.
2008-10-18 | E-GEOD-8584 | biostudies-arrayexpress
Project description:Asymmetric cancer cell division regulated by AKT, Reactive Oxygen Species (ROS) high versus ROS low mRNA
| PRJNA143495 | ENA
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this âAKTlowâ cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated, each in duplicate, using RNA-Seq.
2015-12-09 | E-GEOD-71900 | biostudies-arrayexpress
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this â??AKTlowâ?? cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Secreted protein profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated using antibody arrays.
2015-12-09 | E-GEOD-71892 | biostudies-arrayexpress
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this âAKTlowâ cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Secreted protein profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated using antibody arrays.
2015-12-09 | E-GEOD-71891 | biostudies-arrayexpress
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this â??AKTlowâ?? cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated, each in duplicate, using small RNA-Seq.
2015-12-09 | E-GEOD-71893 | biostudies-arrayexpress
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this âAKTlowâ cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated, each in duplicate, using GRO-Seq.
2015-12-09 | E-GEOD-71898 | biostudies-arrayexpress
Project description:Small-molecule inhibitors of AKT signaling are being in evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with sub-therapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multi-scale, molecular snapshot of this âAKTlowâ cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously up-regulate a host of other proteins and metabolites post-transcriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication. Microvesicle content profiles of MCF7 and HCT116 Akti-1/2 treated cells and MCF7 and HCT116 vehicle (i.e. DMSO) treated cells were generated, using technical replicates, using small RNA-Seq.
2015-12-09 | E-GEOD-71895 | biostudies-arrayexpress