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Wnt5a Signaling Induced Phosphorylation Increases Acyl Protein Thioesterase 1 Activity and Promotes Melanoma Metastatic Behavior / Rochelle Shirin Sadeghi.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Sadeghi, Rochelle Shirin, author.
- Language:
- English
- Subjects (All):
- Cellular biology.
- Molecular biology.
- Oncology.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Local Subjects:
- Cellular biology.
- Molecular biology.
- Oncology.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (109 pages)
- Contained In:
- Dissertation Abstracts International 80-02B(E).
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2018.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood. Wnt5a signaling results in acyl protein thioesterase 1 (APT1) mediated depalmitoylation of pro-metastatic cell adhesion molecules CD44 and MCAM, resulting in increased melanoma invasion. The mechanistic details that underlie Wnt5a-mediated regulation of APT1 activity and cellular function remains unknown. Here, we show Wnt5a signaling regulates APT1 activity through induction of APT1 phosphorylation and we further investigate the functional role of APT1 phosphorylation on its depalmitoylating activity. We found phosphorylation increased APT1 depalmitoylating activity and reduced APT1 dimerization. We further determined APT1 phosphorylation increases melanoma invasion in vitro and is also correlated with increased tumor grade and metastasis. Our results further establish APT1 as an important regulator of melanoma invasion and metastatic behavior. Inhibition of APT1 may represent a novel way to treat Wnt5a driven cancers.
- Notes:
- Source: Dissertation Abstracts International, Volume: 80-02(E), Section: B.
- Advisors: Eric S. Witze; Committee members: Donita C. Brady; Luca Busino; Constantinos Koumenis; Ellen Pure.
- Department: Cell and Molecular Biology.
- Ph.D. University of Pennsylvania 2018.
- Local Notes:
- School code: 0175
- ISBN:
- 9780438423824
- Access Restriction:
- Restricted for use by site license.
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