Wnt5a signaling induced phosphorylation increases APT1 activity and promotes melanoma metastatic behavior
- University of Pennsylvania, United States
- University of Chicago, United States
Abstract
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.
Data availability
All MS-APT1 raw files have been deposited in the CHORUS database under project number 1456 (https://chorusproject.org/).
Article and author information
Author details
Rahul Singh Kathayat
Funding
National Cancer Institute (CA181633)
- Eric Witze
American Cancer Society (RSG-15-027-01)
- Eric Witze
National Institute of Allergy and Infectious Diseases (AI118891)
- Benjamin A Garcia
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Sadeghi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Wnt5a signaling induced phosphorylation increases APT1 activity and promotes melanoma metastatic behavior
eLife 7:e34362.
https://doi.org/10.7554/eLife.34362
