Identification of novel protein tyrosine phosphatases (PTPs) regulating the Hippo pathway in tumorigenesis
Loading...
Authors
SarmastiEmami, Sahar
Date
Type
thesis
Language
eng
Keyword
Hippo pathway , Phosphatases , Protein tyrosine phosphatases , PTP
Alternative Title
Abstract
The Hippo signaling pathway is a tumor suppressor pathway which plays key roles in normal organ size control through regulation of cell proliferation and cell death. Deregulation of the Hippo pathway leads to excessive cell proliferation and loss of cell contact inhibition, which is observed in tumorigenesis and metastasis. Although the regulation of the Hippo pathway by protein kinases is extensively studied, how the Hippo pathway is regulated by protein phosphatases is largely unknown.
In this study, we first did a screening by using a LATS biosensor (LATS-BS), a YAP /TAZ activity reporter (STBS-Luc) and a PTP (Protein Tyrosine Phosphatase) library. Based on the result of two parallel screenings, I have identified many novel PTP regulators of the Hippo pathway. Further experiments were performed to validate the result of the screening. Of all candidates, PTPN12 was selected for further study as it is a tumor suppressor gene that is mutated in a variety of cancers including breast cancer. Recently PTPN12 was shown to play a role as a master regulator of oncogenic Receptor Tyrosine kinases (RTKs), therefore it is a novel regulator of the Hippo pathway in breast cancer cells.
We further demonstrated that PTPN12 regulates the Hippo pathway through inhibition of the oncogenic function of the main effector of the Hippo pathway, YAP. Interestingly, we demonstrated that loss of PTPN12 increases cell proliferation in MCF10A mammary cells in a Hippo-dependent manner. Altogether, our findings provide useful information on the roles of PTP-Hippo interactions in breast cancer biology and therapy.
Description
Citation
Publisher
License
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.