PXD059013

PXD059013 is an original dataset announced via ProteomeXchange.

Title	Human colon cancer cell lines - LC-MSMS
Description	Despite the advent of mutant-selective KRAS inhibitors, colorectal cancer (CRC) responses remain limited, with frequent stable disease and rapid recurrence. The mechanisms underlying CRC tolerance to KRAS inhibition and eventual resistance are poorly understood. Here, we explored early transcriptional and proteomic changes following KRAS silencing in 3D CRC spheroid models to identify pathways linked to sensitivity or resistance. Based on growth, cell cycle, and apoptosis responses, cell lines were classified as KRAS silencing-sensitive (HCT116, SW480) or -resistant (LS174T, SW837). Sensitive cells showed upregulation of the unfolded protein response (UPR) and WNT/β-catenin signaling, while these pathways were downregulated in resistant cells. Proteomic analysis confirmed UPR deregulation, with reduced translation-related proteins in sensitive cells. Functional assays revealed that KRAS knockdown in HCT116 reduced protein aggregation and translational capacity, consistent with UPR activation. However, inhibiting IRE1α-mediated UPR signaling did not reverse KRAS silencing-induced arrest or apoptosis. These findings suggest UPR activation as an early adaptive response in KRAS-dependent CRC cells.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_06:03:04.950.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059013
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rune Matthiesen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-18 14:27:24	ID requested
⏵ 1	2025-05-07 06:03:05	announced

10.1038/s41598-025-94549-2;

Martins F, Machado AL, Carvalho J, Almeida CR, Beck HC, Carvalho AS, Backman V, Matthiesen R, Velho S, Differential unfolded protein response regulation in KRAS silencing sensitive and innately resistant colorectal cancer cells. Sci Rep, 15(1):14329(2025) [pubmed]

10.6019/PXD059013;

submitter keyword: Human, LC-MSMS, resistant, colon cancer, KRAS silencing

Rune Matthiesen
contact affiliation	Computational and Experimental Biology Group NOVA MEDICAL SCHOOL / FACULDADE DE CIÊNCIAS MÉDICAS UNIVERSIDADE NOVA DE LISBOA Rua Câmara Pestana, 6-6A | 1150-082 Lisboa Portugal
contact email	runem2009@gmail.com
lab head
Rune Matthiesen
contact affiliation	Computational and Experimental Biology Group, CEDOC NOVA MEDICAL SCHOOL / FACULDADE DE CIÊNCIAS MÉDICAS UNIVERSIDADE NOVA DE LISBOA Rua Câmara Pestana, 6-6A | 1150-082 Lisboa Portugal
contact email	runem2009@gmail.com
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/2025/05/PXD059013

PRIDE project URI

• PRIDE
  1. PXD059013
     1. Label: PRIDE project
     2. Name: Human colon cancer cell lines - LC-MSMS