Dicer1 Phosphomimetic Promotes Tumor Progression and Dissemination

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 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and because this pathway is...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2019-05, Vol.79 (10), p.2662-2668
Main Authors: Aryal, Neeraj K, Pant, Vinod, Wasylishen, Amanda R, Rimel, Bobbie J, Baseler, Laura, El-Naggar, Adel K, Mutch, David G, Goodfellow, Paul J, Arur, Swathi, Lozano, Guillermina
Format: Article
Language:English
Subjects:
Animals
Carcinogenesis - genetics
DEAD-box RNA Helicases - genetics
Disease Models, Animal
Disease Progression
MAP Kinase Signaling System - genetics
Mice
Mice, Inbred C57BL
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Neoplasms - genetics
Neoplasms - pathology
Phosphorylation - genetics
Ribonuclease III - genetics
Signal Transduction - genetics
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Summary: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 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 ( and ). 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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-18-2460