PXD054001

PXD054001 is an original dataset announced via ProteomeXchange.

Title	Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model
Description	Circulating tumor cells (CTCs) play an important role in metastasis formation. Aberrant signaling of oncogenic pathways (e.g. PI3K/AKT/mTOR pathway) drives tumor progression. In this work, the susceptibility of the colon cancer CTC derived cell line, CTC-MCC-41, for AKT and mTOR inhibitors was evaluated. Additionally, the functional role of the expressed AKT isoforms was characterized in this cell line. The efficacy of AKT inhibitor MK2206, the mTOR inhibitor RAD001 and the combination was examined in CTC-MCC-41 cells in a murine intracardiac xenotransplantation model. Furthermore, stable isoform specific AKT1 or AKT2 knockdowns (KD) as well as AKT1/AKT2 double KD cells were generated. Differentially regulated proteins and phospho-peptides were identified using LC-MS. CTC-MCC-41 cells show a high susceptibility for dual targeting of AKT and mTOR in vivo indicating that selective eradication of CTCs may be considered as a new treatment option in cancer. KD of AKT1 or AKT2 significantly reduced the proliferation of CTC-MCC-41 cells. AKT KDs share commonly regulated proteins and phospho-proteins, but also regulate a large number uniquely. AKT1/AKT2 double KD cells show a strongly dysregulated replication machinery, as well as a decrease in cell cycle activity and stem cell associated processes underlining the non-redundant role of AKT isoforms.
HostingRepository	PRIDE
AnnounceDate	2025-04-14
AnnouncementXML	Submission_2025-04-14_04:33:25.617.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Mair
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-17 02:53:19	ID requested
⏵ 1	2025-04-14 04:33:29	announced

10.1002/1878-0261.70024;

Smit DJ, Pereira-Veiga T, Brauer H, Horn M, Nissen P, Mair T, Siebels B, Vo, ß H, Zhuang R, Haider MT, Loreth D, Iskhakova M, Lindemann B, K, ö, tt J, Cayrefourcq L, Wellbrock J, Schl, ü, ter H, Pantel K, Alix-Panabi, è, res C, J, ü, cker M, Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model. Mol Oncol, ():(2025) [pubmed]

submitter keyword: CTCs

PI3K/AKT/mTOR pathway

AKT isoforms

xenotransplantation model

proteomics

MK2206

RAD001

colorectal carcinoma

drug sensitivity assays

dual targeting

personalized medicine

targeted therapy

Daniel J. Smit, MD, PhD
contact affiliation	Institute of Tumor Biology University Medical Center Hamburg-Eppendorf Martinistraße 52, 20246 Hamburg, Germany
contact email	d.smit@uke.de
lab head
Thomas Mair
contact affiliation	Section for Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
contact email	t.mair@uke.de
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/2025/04/PXD054001

PRIDE project URI

• PRIDE
  1. PXD054001
     1. Label: PRIDE project
     2. Name: Targeting the AKT/mTOR pathway attenuates the metastatic potential of colorectal carcinoma circulating tumor cells in a murine xenotransplantation model