PXD060045-1

PXD060045 is an original dataset announced via ProteomeXchange.

Title	Pharmacological Targeting of DHHC9-Mediated STRN4 Palmitoylation to Suppress YAP-Driven Cancer Metastasis
Description	Protein S-palmitoylation, a dynamic and reversible post-translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signaling. Dysregulation of this modification has emerged as a critical driver of cancer progression, influencing oncogenes and signaling pathways. Among the 23 DHHC palmitoyl transferases responsible for catalyzing S-palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets. However, the cancer-specific roles and substrates of individual DHHC enzymes remain poorly characterized. In this study, we identified DHHC9 as a crucial regulator of adenocarcinoma progression, including colorectal and lung cancers. Functional studies demonstrated that DHHC9 knockdown profoundly inhibited cell migration in vitro and tumor metastasis in vivo. Proteomic analysis revealed STRN4, a core component of the STRIPAK complex, as a DHHC9-specific substrate whose palmitoylation promotes YAP nuclear localization and activates Hippo pathway effectors CCN1, CCN2, and ANKRD1, driving cancer cell migration. Notably, we discovered two small molecules, treprostinil and 10-HCPT, as potent DHHC9 inhibitors that effectively suppressed adenocarcinoma cell migration. Our findings illuminate a pivotal role for DHHC9 in adenocarcinoma metastasis and unveil its potential as a highly promising therapeutic target in cancer treatment, opening new avenues for intervention in palmitoylation-driven malignancies.
HostingRepository	PRIDE
AnnounceDate	2025-09-15
AnnouncementXML	Submission_2025-09-14_17:01:09.061.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	yang Tian
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N-ethylmaleimide derivatized cysteine; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-21 22:54:02	ID requested
⏵ 1	2025-09-14 17:01:09	announced

10.1111/jcmm.70815;

Tian Y, Li W, Zhai Q, Yu Y, Yuan J, Ma Y, Yang J, Li M, Chang W, Li W, Huang K, Sun C, Zeng C, Sun Y, Gu J, Zhang H, Li D, Yu Y, Hu L, Zhang P, Ma B, Zheng J, Li P, Guo F, Sun Y, Pharmacological Targeting of DHHC9-Mediated STRN4 Palmitoylation to Suppress YAP-Driven Cancer Metastasis. J Cell Mol Med, 29(17):e70815(2025) [pubmed]

ProteomeXchange project tag: Human Proteome Project

submitter keyword: Human,proteomics, protein S-palmitoylation

Yang Sun
contact affiliation	1 Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. 2 Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China. 3 State Key Laboratory Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
contact email	yangsun@xzhmu.edu.cn
lab head
yang Tian
contact affiliation	XuZhou Medical university
contact email	yangtian@xzhmu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060045
     1. Label: PRIDE project
     2. Name: Pharmacological Targeting of DHHC9-Mediated STRN4 Palmitoylation to Suppress YAP-Driven Cancer Metastasis