PXD066045

PXD066045 is an original dataset announced via ProteomeXchange.

Title	Methyltransferase-like 3 (METTL3) regulates exocytosis
Description	RNA modification pathways are often mis-regulated in various typers of cancer, with N6-methyladenosine (m6A) playing a pivotal role in cancer progression and metastasis. Methyltransferase-like 3 (METTL3), a core component of the m6A methyltransferase complex, functions not only as an m6A writer but also promotes tumorigenesis through m6A-independent mechanisms. Here, we show that METTL3 is mislocalized to the cytoplasm in breast cancer tumors from patients, contributing to the oncogenic phenotype. Cytoplasmic METTL3 interacts with EXOC7, a key exocytosis regulator. Additionally, METTL3 regulates m6A-dependent alternative splicing (AS) of EXOC7, promoting the expression of a more aggressive isoform. Silencing METTL3 impairs vesicle trafficking and alters the breast cancer secretome. These effects arenot dependent on its enzymatic activity but instead associated with METTL3-mediated stabilization of EXOC7. Furthermore, knockdown of METTL3 , but not inhibition of its catalytic function, impairs invadopodia formation, collagen matrix invasion, and the generation of focal adhesions , all of which are critical for extracellular matrix degradation and cell invasion. Our findings uncover non-catalytic roles of METTL3 in regulating exocytosis and the cancer secretome, with broader implications for other cancer types.
HostingRepository	PRIDE
AnnounceDate	2026-05-04
AnnouncementXML	Submission_2026-05-04_03:41:12.912.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andreas Pich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	S-carboxamidoethyl-L-cysteine; acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-11 00:42:24	ID requested
⏵ 1	2026-05-04 03:41:14	announced

Dataset with its publication pending

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: EXOC7, breast cancer,RNA modification, vesicle trafficking, exocyst, N6-methyladenosine, METTL3

Andreas Pich
contact affiliation	Hannover Medical School Institute of Toxicology Carl-Neuberg-Str. 1 30625 Hannover Germany
contact email	pich.andreas@mh-hannover.de
lab head
Andreas Pich
contact affiliation	Hannover Medical School Core Facility Proteomics
contact email	pich.andreas@mh-hannover.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066045
     1. Label: PRIDE project
     2. Name: Methyltransferase-like 3 (METTL3) regulates exocytosis