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THE ROLE OF NHERF1/EBP50 IN WNT SIGNALING IN THE EPITHELIUM

Treat, Anny (2015) THE ROLE OF NHERF1/EBP50 IN WNT SIGNALING IN THE EPITHELIUM. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

The Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) is a PDZ-domain containing scaffold abundantly expressed in epithelial tissues. Previous reports from our laboratory demonstrate that NHERF1 negatively regulates Wnt canonical signaling in breast epithelial cells through its interactions with Frizzled receptors. Parallel studies conducted at that time also suggested that NHERF1 knockout mice presented a form of communicating hydrocephalus reminiscent of phenotypes associated with mutations in the non-canonical Wnt Planar Cell Polarity (Wnt PCP) pathway. This observation leads to the hypothesis that NHERF1 regulates both canonical and non-canonical Wnt signaling and acts as a “signaling switch” between the two pathways. To further elucidate the role of NHERF1 in Wnt signaling regulation we proposed three specific aims: 1) To demonstrate that NHERF1 can act as a tumor suppressor in a Wnt/β-catenin driven breast cancer model, 2) To determine the role of NHERF1 expression and Wnt/β-catenin in endocrine resistant breast cancer, and 3) Investigate the role of NHERF1 in the regulation of Wnt PCP signaling in the mouse ependyma. Although the exact role that NHERF1 plays in the regulation of Wnt canonical signaling in breast cancer remains elusive, our results indicate that NHERF1 increases the association of key Wnt PCP members Van-Gogh like (Vangl) and Frizzled (Fzd) and promotes PCP signaling and ciliogenesis in mouse ependymal tissue.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Treat, Annyannytreat@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairOesterreich, Steffisto16@pitt.eduSTO16
Thesis AdvisorRomero, Guillermoggr@pitt.eduGGR
Committee MemberAltschuler, Davidaltschul@pitt.eduALTSCHUL
Committee MemberFriedman, Peterpaf10@pitt.eduPAF10
Committee MemberBrufsky, Adamadb5@pitt.eduADB5
Committee MemberMonga, Satdarshan P. S.smonga@pitt.eduSMONGA
Date: 16 December 2015
Date Type: Publication
Defense Date: 1 October 2015
Approval Date: 16 December 2015
Submission Date: 10 December 2015
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 150
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Pharmacology and Chemical Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: NHERF1, EBP50, Wnt signaling, Planar Cell Polarity, ciliogenesis, breast cancer, endocrine resistance
Date Deposited: 16 Dec 2015 17:31
Last Modified: 16 Dec 2016 06:15
URI: http://d-scholarship.pitt.edu/id/eprint/26650

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