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Full-Text Articles in Medical Molecular Biology
Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro
Role Of Phosphorylated Dicer1 In Tumor Progression, Raisa Reyes-Castro
Dissertations & Theses (Open Access)
DICER1 is a multidomain enzyme discovered and widely recognized for its function in small non-coding microRNA (miRNA) synthesis. In cancer development, DICER1 functions as a haploinsufficient tumor suppressor which regulates miRNAs and Epithelial-to-Mesenchymal Transition (EMT). The Arur laboratory discovered that DICER1 is phosphorylated by active ERK and that ERK-mediated phosphorylation triggers DICER1 to translocate from the cytoplasm to the nucleus of cells in worms, mice and humans. Further, a heterozygous allele of a genetically engineered mouse model of phosphomimetic Dicer1 when combined with heterozygous Kras oncogenic background contributes to lung tumor progression in vivo. Mechanisms through which phosphomimetic Dicer1 …
Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz
Molecular Mechanisms Of Prdm16 As A Tumor Suppressor In Pancreatic Ductal Adenocarcinoma, Eric Hurwitz
Theses and Dissertations
The transcription factor Prdm16 functions as a potent suppressor of transforming growth factor-beta (TGF-b) signaling, whose inactivation is deemed essential to the progression of pancreatic ductal adenocarcinoma (PDAC). Using the KrasG12D-based mouse model of human PDAC, we surprisingly found that ablating Prdm16 did not block but instead accelerated PDAC formation and progression, suggesting that Prdm16 might function as a tumor suppressor in this malignancy. Subsequent genetic experiments showed that ablating Prdm16 along with Smad4 resulted in a shift from a well-differentiated and confined neoplasm to a highly aggressive and metastatic disease, which was associated with a striking deviation …