# Targeting ZDHHC13-activated palmitoylation for melanoma treatment

> **NIH NIH R00** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $248,999

## Abstract

PROJECT SUMMARY/ABSTRACT
Melanoma is the deadliest form of skin cancer and is one of the most difficult cancer to treat. Therefore, the
underlying mechanism of melanomagenesis and melanoma development demands intensive study. Recent
findings identified that palmitoylation of melanocortin-1 receptor (MC1R), primarily mediated by the protein-acyl
transferase (PAT) ZDHHC13, is essential for activating MC1R signaling and prevent melanomagenesis.
Preliminary studies also revealed that APT2 is the major depalmitoylating enzyme of MC1R and is harmful for
metastatic melanoma patients. In this proposed study, I aim to elucidate the in-depth molecular mechanism by
which ZDHHC13/APT2-regulated palmitoylation repress melanoma development and progression, and test the
hypothesis that ZDHHC13/APT2-regulated palmitoylation is essential for melanomagenesis and melanoma
metastasis in vivo. During the mentored K99 phase, I will elucidate the underlying regulatory mechanism of
ZDHHC13 in melanocytes by using new developed ZDHHC13 transgenic mice. I will also characterize the effects
of depalmitoylation inhibition in melanomagenesis by targeting APT2. During the independent R00 phase, I plan
to determine the role of ZDHHC13/APT2-regulated palmitoylation in melanoma metastasis in vivo and identify
whether inhibition of depalmitoylation improves survival by suppressing metastasis. Furthermore, I will need
additional trainings during the award period in melanoma mouse model, targeted therapy, as well as professional
skills which will contribute to my long term career goal. In summary, successful completion of my proposed
studies will bring novel insights into the roles and molecular mechanisms of ZDHHC13/APT2-regulated
palmitoylation in melanoma development and progression, which can be translated into new intervention and
treatment strategies. Receipt of this award will allow me to expand my research plan and serve as a platform for
me to receive additional trainings, thus prepare myself becoming an independent principal investigator in the
field of melanoma research.

## Key facts

- **NIH application ID:** 10465250
- **Project number:** 5R00CA234097-04
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Shuyang Chen
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $248,999
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465250

## Citation

> US National Institutes of Health, RePORTER application 10465250, Targeting ZDHHC13-activated palmitoylation for melanoma treatment (5R00CA234097-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10465250. Licensed CC0.

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