Dicer1 phosphomimetic promotes tumor progression and dissemination

Neeraj K. Arya, Vinod Pant, Amanda R. Wasylishen, Bobbie J. Rimel, Laura Baseler, Adel K. El-Naggar, David G. Mutch, Paul J. Goodfellow, Swathi Arur, Guillermina Lozano

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults, and patients with DICER1 syndrome with DICER1 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and because this pathway is activated in human cancers, we asked whether phosphorylated Dicer1 contributed to tumor development. In human endometrioid cancers, we discovered that phosphorylated DICER1 is significantly associated with invasive disease. To test a direct involvement of Dicer1 phosphorylation in tumor development, we studied mice with phosphomimetic alterations at the two conserved serines phosphorylated by ERK and discovered that a phosphomimetic Dicer1 drives tumor development and dissemination in two independent murine cancer models (KRas+/LA1 and p53+/-). Our findings demonstrate that phosphomimetic Dicer1 promotes tumor development and invasion. Significance: This work highlights the relevance of Dicer1 phosphorylation in mammalian tumor development and dissemination.

Original languageEnglish
Pages (from-to)2662-2668
Number of pages7
JournalCancer research
Volume79
Issue number10
DOIs
StatePublished - 2019

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