PXD068486

PXD068486 is an original dataset announced via ProteomeXchange.

Title	Interactomics analysis of SLAP in colorectal cancer cells
Description	The mechanistic target of rapamycin complex 2 (mTORC2) signaling pathway, which regulates cell growth and migration, exhibits oncogenic function in colorectal cancer (CRC). mTORC2 signaling is primarily activated by a complex assembly of mTOR, RICTOR, SIN1, and mLST8, but how dysregulation of this mechanism contributes to its oncogenic function remains elusive. Here, we show that the Src-Like Adaptor Protein (SLAP), a negative regulator of tyrosine kinase signaling receptors, controls mTORC2 integrity to mediate its tumor-suppressive function in CRC. Mechanistically, SLAP interacts with mLST8 and facilitates its non-degradative ubiquitination at lysines 86 and 215, thereby reducing mTORC2 integrity and mTORC2-AKT signaling. The E3 ubiquitin ligase UBE3C was identified as a novel SLAP interactor involved in this ubiquitination process. Functionally, SLAP inhibition of CRC cell growth and invasion was dependent upon mTORC2 signaling inhibition. In immunodeficient mice CRC xenografts, SLAP depletion enhanced mTORC2 activity and sensitized CRC cells to mTOR catalytic inhibitors. Together, our findings reveal a previously unrecognized SLAP–UBE3C–mLST8 axis that regulates mTORC2 integrity and suggest a potential therapeutic avenue for targeting mTORC2 in CRC.
HostingRepository	PRIDE
AnnounceDate	2026-03-11
AnnouncementXML	Submission_2026-03-11_03:01:55.558.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD068486
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Functional Proteomics Platform FPP
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	6x(13)C; 6x(13)C; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap XL; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-18 06:08:42	ID requested
⏵ 1	2026-03-11 03:01:56	announced

10.6019/PXD068486;

Mevizou R, Naim D, Cauchois F, Naudin C, Greaves G, Espie K, Felipe B, Simon V, Boublik Y, Nguyen J, Urbach S, Roche S, Sirvent A, SLAP controls mTORC2 integrity via UBE3C-mediated non-degradative mLST8 ubiquitination to suppress colorectal tumorigenesis. Cell Death Differ, ():(2025) [pubmed]

10.1038/s41418-025-01633-1;

submitter keyword: Human, cancer, SILAC, colon

Serge ROCHE
contact affiliation	CRBM institute, UMR5237 CNRS, France
contact email	Serge.roche@crbm.cnrs.fr
lab head
Functional Proteomics Platform FPP
contact affiliation	FPP CNRS
contact email	contact@fpp.cnrs.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD068486

PRIDE project URI

• PRIDE
  1. PXD068486
     1. Label: PRIDE project
     2. Name: Interactomics analysis of SLAP in colorectal cancer cells