PgmNr D1100: Pointed/ETS acts as a novel tumor suppressor that regulates Ras-mediated cellular senescence.

Authors:
T. Ito ¹ ; M. Enomoto ¹ ; T. Igaki ^1,2

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Institutes
1) Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Kyoto, Japan; 2) PRESTO, Japan Science and Technology Agency (JST), Saitama, Japan.

Keyword: tumor suppressors and oncogenes

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Abstract:

Oncogenic activation of Ras is often not sufficient for driving malignant progression, because it can cause premature senescence. This suggests that mutations in the regulators of cellular senescence could cooperate with oncogenic Ras to drive tumor progression. Here, we performed a genetic screen in Drosophila eye imaginal discs to identify dominant mutations that cause tumor progression in conjunction with oncogenic Ras (Ras^V12). Using the MARCM technique, we induced mosaic expression of Ras^V12 in the eye discs and simultaneously introduced a series of heterozygous chromosomal deficiencies. As a result, we identified a mutation in the ETS transcriptional activator Pointed (Pnt) as a strong dominant-enhancer of Ras^V12-induced tumorigenesis. In addition, overexpression of Pnt dramatically inhibited Ras^V12-induced tumor overgrowth. Interestingly, we found that loss of Pnt abrogated Ras^V12-induced cellular senescence. Our data show that Pnt acts as a novel tumor-suppressor that regulates Ras-mediated cellular senescence in Drosophila.