E-GEOD-23930
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA130421
PROVIDER: E-GEOD-23930 | ExpressionAtlas | 2015-08-12
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:MKK2 is sufficient but not necessary for proliferation and anchorage-independent growth of SK-MEL-28 cells.
| PRJNA130421 | ENA
Project description:Though mitogen activated protein kinase kinases (MKK or MEK) 1 and 2 are widely assumed to be functionally redundant some reports indicate they possess distinct biologic activities. To test the hypothesis that MEK1 and MEK2 signaling pathways are interchangeable we used two complementary approaches to determine the necessity and sufficiency of individual MEK1 and MEK2 signaling pathways for human melanoma SK-MEL-28 cell proliferation. To test the necessity we targeted MEK1 and/or MEK2 using specific siRNAs. An effect on proliferation was observed only when both MEK1 and MEK2 were knocked down indicating that neither of the individual MEK isoforms is necessary for SK-MEL-28 cell proliferation. To test the sufficiency we inhibited multiple MEK and MKK signaling pathways in SK-MEL-28 cells with anthrax lethal toxin (LeTx) a MEK/MKK-specific protease and rescued individual MEK signaling pathways by expressing a cleavage-resistant form of MEK (MEKcr). In this fashion ERK activation was retained only in MEK2cr-expressing cells but not in MEK1cr-expressing cells following LeTx treatment. Microarray analysis revealed groups of non-overlapping downstream transcriptional targets of MEK1 and MEK2 and indicated a substantial rescue effect of MEK2cr on proliferation pathways. Furthermore LeTx efficiently inhibited the cell proliferation and anchorage-independent growth of SK-MEL-28 cells expressing MKK1cr but not MEK2cr. These results not only indicate that in this cellular context MEK2 signaling pathway alone is sufficient for ERK activation melanoma cell proliferation and anchorage-independent growth but MEK1 is not but also demonstrate that MEK1 and MEK2 signaling pathways are not redundant and interchangeable for melanoma cell proliferation. We conclude that while MEK2 alone is sufficient for SK-MEL-28 cell proliferation MEK1 can conditionally compensate for loss of MEK2. SK-MEL-28 melanoma cells +/- cleavage resistant MKK1/MKK2
2011-06-24 | E-GEOD-23930 | biostudies-arrayexpress
Project description:Though mitogen activated protein kinase kinases (MKK or MEK) 1 and 2 are widely assumed to be functionally redundant some reports indicate they possess distinct biologic activities. To test the hypothesis that MEK1 and MEK2 signaling pathways are interchangeable we used two complementary approaches to determine the necessity and sufficiency of individual MEK1 and MEK2 signaling pathways for human melanoma SK-MEL-28 cell proliferation. To test the necessity we targeted MEK1 and/or MEK2 using specific siRNAs. An effect on proliferation was observed only when both MEK1 and MEK2 were knocked down indicating that neither of the individual MEK isoforms is necessary for SK-MEL-28 cell proliferation. To test the sufficiency we inhibited multiple MEK and MKK signaling pathways in SK-MEL-28 cells with anthrax lethal toxin (LeTx) a MEK/MKK-specific protease and rescued individual MEK signaling pathways by expressing a cleavage-resistant form of MEK (MEKcr). In this fashion ERK activation was retained only in MEK2cr-expressing cells but not in MEK1cr-expressing cells following LeTx treatment. Microarray analysis revealed groups of non-overlapping downstream transcriptional targets of MEK1 and MEK2 and indicated a substantial rescue effect of MEK2cr on proliferation pathways. Furthermore LeTx efficiently inhibited the cell proliferation and anchorage-independent growth of SK-MEL-28 cells expressing MKK1cr but not MEK2cr. These results not only indicate that in this cellular context MEK2 signaling pathway alone is sufficient for ERK activation melanoma cell proliferation and anchorage-independent growth but MEK1 is not but also demonstrate that MEK1 and MEK2 signaling pathways are not redundant and interchangeable for melanoma cell proliferation. We conclude that while MEK2 alone is sufficient for SK-MEL-28 cell proliferation MEK1 can conditionally compensate for loss of MEK2.
2011-06-24 | GSE23930 | GEO
Project description:Hypothesis: Overexpression of the GLUT1 facilitative glucose transporter, in A7r5 vascular smooth muscle cells, is sufficient and/or necessary to induce alterations in gene expression which influence apoptosis, growth, and proliferation.
2009-10-23 | GSE15713 | GEO
Project description:Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fuelled by the tumor cell’s ability to ‘secrete-and-sense’ growth factors; this translates into cell survival and proliferation that is self-sustained by auto-/paracrine secretion. Using breast cancer cells that are either endowed or impaired in growth signaling autonomy, here we reveal how autonomy impacts cancer progression. Autonomy is associated with enhanced molecular programs for stemness, immune evasiveness, proliferation, and epithelial-mesenchymal plasticity (EMP). Autonomy is both necessary and sufficient for anchorage-independent growth factor-restricted proliferation and resistance to anti-cancer drugs and is required for metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated with self-sustained EGFR/ErbB signaling. A gene expression signature is derived (a.k.a., autonomy signature) which revealed that autonomy is induced in circulating tumor cells (CTCs) and particularly CTC clusters, the latter of which carry higher metastatic potential. Autonomy in CTCs tracks therapeutic response and prognosticates outcome. Autonomy is preserved during reversible (but not stable) EMT. These data support a role for growth signaling autonomy in multiple processes essential for the blood-borne dissemination of human breast cancer.
2023-06-20 | GSE215822 | GEO
Project description:Self-sufficiency (autonomy) in growth signaling, the earliest recognized hallmark of cancer, is fuelled by the tumor cell’s ability to ‘secrete-and-sense’ growth factors; this translates into cell survival and proliferation that is self-sustained by auto-/paracrine secretion. Using breast cancer cells that are either endowed or inept in growth signaling autonomy, here we reveal how tumor cell autonomy impacts cancer progression. Autonomy is associated with enhanced molecular programs for stemness, immune evasiveness, and epithelial-mesenchymal plasticity (EMP) across the entire mesenchymal spectrum. Autonomy is both necessary and sufficient for anchorage-independent growth factor-restricted growth, resistance to anti-cancer drugs and metastatic progression. Transcriptomic and proteomic studies show that autonomy is associated with self-sustained EGFR/ERBB signaling, a required signal for re-epithelialization. A gene expression signature was derived (a.k.a., autonomy signature) which revealed that autonomy is induced in circulating tumor cells (CTCs), the precursor tumor cells that re-epithelialize to initiate metastases. Autonomy in CTCs tracks therapeutic response and prognosticates outcome. Autonomy is present during reversible (but not stable) EMT and requires EGFR/ERBB signaling. These data support a role for growth signaling autonomy in the blood-borne dissemination of human breast cancer.
2023-02-06 | PXD037253 | Pride
Project description:To discover novel growth factors for hematopoietic stem- and progenitor cells (HSPCs), we have assessed cytokine responses of cord blood (CB)-derived CD34+ cells in a high-content growth factor screen. We identify the immunoregulatory chemokine (C-C motif) ligand 28 (CCL28) as a novel growth factor that directly stimulates proliferation of primitive hematopoietic cells from different ontogenetic origins. Microarrays are used to compare the expression profiles of HSPCs expanded in SCF, TPO and CCL28 respectively.
2013-06-03 | GSE45136 | GEO
Project description:Reversible and irreversible anchorage independent growth in skin cells
| PRJNA110237 | ENA
Project description:<p>Solute carrier (SLC) transporters control fluxes of nutrients and metabolites across membranes and thereby represent a critical interface between the microenvironment and cellular and subcellular metabolism. Because of substantial functional overlap, the interplay and relative contributions of SLCs in response to environmental stresses remain poorly elucidated. To infer functional relationships between SLCs and metabolites, we developed a strategy to identify SLCs able to sustain cell viability and proliferation under growth-limiting concentrations of essential nutrients. One-by-one depletion of 13 amino acids required for cell proliferation enabled gain-of-function genetic screens using a SLC-focused CRISPR/Cas9–based transcriptional activation approach to uncover transporters relieving cells from growth-limiting metabolic bottlenecks. Among the transporters identified, we characterized the cationic amino acid transporter SLC7A3 as a gene that, when up-regulated, overcame low availability of arginine and lysine by increasing their uptake, whereas SLC7A5 was able to sustain cellular fitness upon deprivation of several neutral amino acids. Moreover, we identified metabolic compensation mediated by the glutamate/aspartate transporters SLC1A2 and SLC1A3 under glutamine-limiting conditions. Overall, this gain-of-function approach using human cells uncovered functional transporter-nutrient relationships and revealed that transport activity up-regulation may be sufficient to overcome environmental metabolic restrictions.</p>
2022-09-20 | MTBLS4268 | MetaboLights