UZH-Logo

Maintenance Infos

A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis


Abstract

Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2(Δ8,9)) promotes development of melanoma in mouse models. Atf2(Δ8,9)-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2(Δ8,9), we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2(SV5)) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2(SV5) expression is elevated in human melanoma specimens and is associated with poor prognosis. These findings point to an oncogenic function for ATF2 in melanoma development that appears to be independent of its transcriptional activity.

Abstract

Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2(Δ8,9)) promotes development of melanoma in mouse models. Atf2(Δ8,9)-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2(Δ8,9), we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2(SV5)) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2(SV5) expression is elevated in human melanoma specimens and is associated with poor prognosis. These findings point to an oncogenic function for ATF2 in melanoma development that appears to be independent of its transcriptional activity.

Altmetrics

Downloads

5 downloads since deposited on 12 Jul 2016
5 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:31 May 2016
Deposited On:12 Jul 2016 09:03
Last Modified:13 Jul 2016 08:14
Publisher:Elsevier
ISSN:2211-1247
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.celrep.2016.04.072
PubMed ID:27210757

Download

[img]
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations