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Identification of cell surface proteins in Zdhhc20 KO cells

ABSTRACT: An shRNA screen to search for the mediators of pancreatic cancer metastasis identified palmitoyl transferase ZDHHC20 as a protein that mediates this process by promoting the outgrowth of metastatic cells in vivo, We generated a KO of Zdhhc20 using Cas9/CRISPR and sought to determine the changes in the cell surface proteome in KO cells versus parental cells.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Pancreatic Duct

DISEASE(S): Pancreatic Cancer

SUBMITTER: Goran Tomic

LAB HEAD: Julian Downward

PROVIDER: PXD038384 | Pride | 2023-02-09

REPOSITORIES: Pride

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			Action	DRS
	20210420_BR2183_E4_R1.raw	Raw
	20210420_BR2183_E4_R2.raw	Raw
	20210420_BR2183_E4_R3.raw	Raw
	20210420_BR2183_PAR_R1.raw	Raw
	20210420_BR2183_PAR_R2.raw	Raw

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Project description:Post-translational modifications of malignant transformation and tumor maintenance in pancreatic ductal adenocarcinoma (PDAC) in the context of KRAS signaling remains largely unexplored. Here, we used the KPC mouse model to examine the effect of palmitoylation on pancreatic cancer progression. ZDHHC20, upregulated by KRAS, is abnormally overexpressed and associated with poor prognosis in patients with pancreatic cancer. Dysregulation of ZDHHC20 promotes pancreatic cancer progression in a palmitoylation-dependent manner. ZDHHC20 inhibits lysosomal localization and degradation of YTHDF3 through S-palmitoylation of Cys474, which can result in abnormal accumulation of the oncogenic product MYC and thereby promote the malignant phenotypes of cancer cells. Further, we designed a biologically active YTHDF3-derived peptide to competitively inhibit YTHDF3 palmitoylation mediated by ZDHHC20, which in turn downregulated MYC expression and inhibited the progression of KRAS mutant pancreatic cancer. Thus, these findings highlight the therapeutic potential of targeting the ZDHHC20-YTHDF3-MYC signaling axis in pancreatic cancer.

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RNAseq of murine MB49 tumors - WT and gal-9-KO - grown on C57BL/6 syngenic mice through serial transplantations

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