Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
METTL3 regulates exocytosis independently of m6A
Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0002-8047-9298
Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0009-0007-6151-8048
Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0003-0997-5958
Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0009-0005-2931-7794
Show others and affiliations
2026 (English)In: Science Advances, E-ISSN 2375-2548, Vol. 12, no 26, article id eadz2434Article in journal (Refereed) Published
Abstract [en]

RNA modification pathways are often misregulated in various cancers, with N6-methyladenosine (m6A) having a pivotal role in cancer progression and metastasis. Methyltransferase-like 3 (METTL3), a core component of the m6A methyltransferase complex, not only functions 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 regulator of exocytosis, promoting its stabilization. In addition, METTL3 regulates m6A-dependent alternative splicing of EXOC7. Silencing METTL3 impairs vesicle trafficking and the breast cancer secretome-effects that do not rely on its enzymatic activity but instead involve METTL3-mediated stabilization of EXOC7 and potentially other exocyst components. Furthermore, METTL3 knockdown impairs invadopodia formation, collagen matrix invasion, and focal adhesion morphology in vitro, while inhibition of METTL3 catalytic activity does not. Our findings uncover noncatalytic roles of METTL3 in regulating exocytosis and the cancer secretome.

Place, publisher, year, edition, pages
American Association for the Advancement of Science (AAAS), 2026. Vol. 12, no 26, article id eadz2434
National Category
Biochemistry Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-256798DOI: 10.1126/sciadv.adz2434ISI: 001805484300013PubMedID: 42361186Scopus ID: 2-s2.0-105043879357OAI: oai:DiVA.org:umu-256798DiVA, id: diva2:2086826
Funder
Knut and Alice Wallenberg FoundationUmeå UniversityRegion VästerbottenSwedish Research Council, 2017-01636Swedish Research Council, 2022-01322The Kempe Foundations, SMK1766Swedish Cancer Society, 190337 PjSwedish Cancer Society, 22 2455 PjAvailable from: 2026-07-16 Created: 2026-07-16 Last updated: 2026-07-16Bibliographically approved

Open Access in DiVA

fulltext(4528 kB)32 downloads
File information
File name FULLTEXT01.pdfFile size 4528 kBChecksum SHA-512
0554eb6959dfbb48a539cd4105bdaefc0749d9d352d17d0a34ecc553a181381825f76791ace8cee35505c800fc3d80ecab13c507b182c5a2adc547df0a92bcfa
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Esteva-Socias, MargalidaBhattarai, Devi PrasadAchour, CyrinneBaidya, PoonamKumari, KanchanSeier, KerstinPace, HudsonMalla, SandhyaZhu, ShaochunLundin, EvaBally, MartaMateus, AndréAguilo, Francesca

Search in DiVA

By author/editor
Esteva-Socias, MargalidaBhattarai, Devi PrasadAchour, CyrinneBaidya, PoonamKumari, KanchanFontanari, GaiaSeier, KerstinPace, HudsonMalla, SandhyaZhu, ShaochunLundin, EvaBroberg Vågbø, CathrineBally, MartaSwaminathan, VinayMateus, AndréRodriguez-Barrueco, RuthPich, AndreasAguilo, Francesca
By organisation
Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)Department of Molecular Biology (Faculty of Medicine)Department of Clinical MicrobiologyUmeå Centre for Microbial Research (UCMR)Department of ChemistryDepartment of Medical BiosciencesMolecular Infection Medicine Sweden (MIMS)
In the same journal
Science Advances
BiochemistryMolecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 278 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf