Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/33443
Title: THE SIGNALING AND REGULATION OF METASTASIS-ASSOCIATED PHOSPHATASE PRL-3 IN HUMAN CANCER CELLS
Authors: ABDUL QADER OMER AL-AIDAROOS
Keywords: cancer, metastasis, EGFR, oncogene addiction, PTP1B, beta-catenin
Issue Date: 20-Jan-2012
Source: ABDUL QADER OMER AL-AIDAROOS (2012-01-20). THE SIGNALING AND REGULATION OF METASTASIS-ASSOCIATED PHOSPHATASE PRL-3 IN HUMAN CANCER CELLS. ScholarBank@NUS Repository.
Abstract: PRL-3 (phosphatase of regenerating liver-3) has been proposed to play a causal role in metastatic progression of multiple tumor types. However, the signaling mechanism(s) of this oncogene is still poorly defined. Herein, I demonstrate that PRL-3 overexpression results in phospho-activation of EGFR, a phenomenon mediated in part by transcriptional downregulation of PTP1B, an EGFR phosphatase. PRL-3-mediated activation of PI3K/AKT and MAPK pathways, as well as increased cell proliferation, was abolished upon EGFR inhibition, thereby implicating a key role, and potential therapeutic value, of EGFR in PRL-3-mediated oncogenesis. In a separate study in ovarian cancer cells, I showed that PRL-3 inhibited intercellular adhesion, an observation correlated with a pronounced suppression of beta-catenin protein expression. PRL-3 promoted the proteasomal degradation of beta-catenin by enhancing the activity of the Axin/APC degradation complex, likely through beta-catenin regulators Nkd and Dvl. Finally, I investigated the phosphorylation of PRL-3 as a novel method of its regulation.
URI: http://scholarbank.nus.edu.sg/handle/10635/33443
Appears in Collections:Ph.D Theses (Open)

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