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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 29, 2016 |
| Title |
Transcriptionally inactive ATF2 variant drives melanomagenesis [Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Characterized by striking metastatic propensity and chemoresistance, melanoma is among the most lethal cutaneous malignancies. The transcription factor ATF2 was shown to elicit oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, a mouse model engineered to express a transcriptionally inactive form of Atf2 (Atf2?8,9) was found to be sufficient to induce nevi formation and, when crossed with BrafV600E animals, to promote melanoma development. The cross of Atf2?8,9 with BrafV600E;Pten-/- mice augmented pigmentation, tumorigenicity, and metastasis. Similar to mouse Atf2?8,9, the human ATF2 splice variant 5 enhanced growth and migration capacity of cultured melanoma and immortalized melanocytes. Induced Melan-A, CXCL9, S100A8, CCR7 expression, seen in Atf2?8,9-driven tumors associate with their enhanced pigmentation, immune infiltration and propensity to metastasize. Notably, elevated ATF2SV5 expression in melanoma specimens coincided with poor prognosis. The gain-of-function activity elicited by the truncated ATF2 form offers unexpected insight into mechanisms underlying melanoma development and progression.
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| Overall design |
Compared silencing of ATF2SV5 in H3A cells vs. silencing of ATF2WT via Ampliseq whole transcriptome analysis on the Ion Proton
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| Contributor(s) |
Claps G, Cheli Y, Zhang T, Scortegagna M, Lau EL, Kim H, Qi J, Li J, James B, Levesque M, Dummer R, Hayward NK, Bosenberg M, Brown KM, Ronai ZA |
| Citation(s) |
27210757 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA099961 |
ATF2 in melanoma development and progression |
Sanford-Burnham Medical Research Institute |
RONAI |
| P30 CA030199 |
Cancer Center Support Grant (CCSG): Administration (Admin Core): Cancer Center Support Grant: Developmental Funds Core: Planning and Evaluation Core |
Sanford-Burnham Medical Research Institute |
POWIS |
| R01 CA172017 |
ATF2 Oncogenic Addiction in Melanoma |
Sanford-Burnham Medical Research Institute |
RONAI |
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| Submission date |
Apr 04, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
brian james |
| E-mail(s) |
bjames@sanfordburnham.org
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| Organization name |
Sanford Burnham
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| Street address |
10901 North Torrey Pines Road
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| City |
San Diego |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (1) |
| GPL17303 |
Ion Torrent Proton (Homo sapiens) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE81014 |
Transcriptionally inactive ATF2 variant drives melanomagenesis |
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| Relations |
| BioProject |
PRJNA317371 |
| SRA |
SRP072851 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE79917_RAW.tar |
4.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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