Wnt5a signaling induced phosphorylation increases APT1 activity and promotes melanoma metastatic behavior

Autor: Eric S. Witze, Benjamin A. Garcia, Rochelle Sadeghi, Katarzyna Kulej, Bryan C. Dickinson, Rahul S. Kathayat, Donita C. Brady
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Protein Conformation
Regulator
cell lines
Metastasis
0302 clinical medicine
Cell Movement
Tumor Cells
Cultured
palmitoylation
Phosphorylation
Biology (General)
Cancer Biology
biology
Chemistry
Cell adhesion molecule
General Neuroscience
Melanoma
Wnt signaling pathway
General Medicine
WNT5A
Hyaluronan Receptors
030220 oncology & carcinogenesis
Medicine
Research Article
Human
Signal Transduction
QH301-705.5
Lipoylation
Science
CD146 Antigen
Wnt-5a Protein
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
medicine
melanoma
Humans
Neoplasm Invasiveness
Cell Proliferation
General Immunology and Microbiology
CD44
Cell Biology
Wnt5a
medicine.disease
Wnt signaling
030104 developmental biology
biology.protein
Cancer research
Thiolester Hydrolases
Protein Multimerization
Protein Processing
Post-Translational
Zdroj: eLife, Vol 7 (2018)
eLife
Popis: 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 remain 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 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.
Databáze: OpenAIRE
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