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E-GEOD-50004 - Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells

Status
Released on 7 August 2015, last updated on 19 August 2015
Organism
Homo sapiens
Samples (20)
Array (1)
Protocols (7)
Description
We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAF(V600E) mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated β-galactosidase (SA-β-gal), senescence-associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence such as SA-β-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail vein colony-forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance. To better understand the molecular mechanisms governing the response of highly invasive cells to IR as compared to that of poorly invasive cells, we performed microarray analysis of both poorly and highly invasive cells at early and late timepoints after irradiation. Cells were treated with y-irradiation, and RNA was taken at 1 hour, 24 hours and 5 days after irradiation. Microarray analysis was performed using Illumina Human HT-12 ver3 expression arrays, and each time point was compared to RNA from untreated cells.
Experiment type
transcription profiling by array 
Contacts
Alexander Valiga, Amanpreet Kaur, Ana Slipicevic, Andrew V Kossenkov, Ashani T Weeraratna, Dennie T Frederick, Elin Lehrmann, Frederick Keeney, Gao Zhang, Jessica Appleton, Kathryn A Kinzler, Katie Marchbank, Keith T Flaherty, Kevin G Becker, Mai Xu, Marie R Webster, Maureen E Murphy, Meenhard Herlyn, Michael P O’Connell, Michela Perego, Vanessa M Dang, William Wood III, Xiaowei Xu
Citation
Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells. Webster MR, Xu M, Kinzler KA, Kaur A, Appleton J, O'Connell MP, Marchbank K, Valiga A, Dang VM, Perego M, Zhang G, Slipicevic A, Keeney F, Lehrmann E, Wood W 3rd, Becker KG, Kossenkov AV, Frederick DT, Flaherty KT, Xu X, Herlyn M, Murphy ME, Weeraratna AT.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-50004.idf.txt
Sample and data relationshipE-GEOD-50004.sdrf.txt
Processed data (1)E-GEOD-50004.processed.1.zip
Additional data (1)E-GEOD-50004.additional.1.zip
Array designA-MEXP-1171.adf.txt
Links