TY - JOUR
T1 - A Transcriptionally Inactive ATF2 Variant Drives Melanomagenesis
AU - Claps, Giuseppina
AU - Cheli, Yann
AU - Zhang, Tongwu
AU - Scortegagna, Marzia
AU - Lau, Eric
AU - Kim, Hyungsoo
AU - Qi, Jianfei
AU - Li, Jian Liang
AU - James, Brian
AU - Dzung, Andreas
AU - Levesque, Mitchell P.
AU - Dummer, Reinhard
AU - Hayward, Nicholas K.
AU - Bosenberg, Marcus
AU - Brown, Kevin M.
AU - Ronai, Ze'ev A.
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/5/31
Y1 - 2016/5/31
N2 - 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 (Atf2δ8,9) promotes development of melanoma in mouse models. Atf2δ8,9-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2δ8,9, we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2SV5) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2SV5 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.
AB - 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 (Atf2δ8,9) promotes development of melanoma in mouse models. Atf2δ8,9-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2δ8,9, we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2SV5) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes. ATF2SV5 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.
UR - https://www.scopus.com/pages/publications/84971261022
U2 - 10.1016/j.celrep.2016.04.072
DO - 10.1016/j.celrep.2016.04.072
M3 - Article
C2 - 27210757
AN - SCOPUS:84971261022
SN - 2211-1247
VL - 15
SP - 1884
EP - 1892
JO - Cell Reports
JF - Cell Reports
IS - 9
ER -