PXD055521-1

PXD055521 is an original dataset announced via ProteomeXchange.

Title	Analysis of L1CAM-regulated signaling pathways and cellular responses to anti-L1CAM radioimmunotherapy in human ovarian cancer cells
Description	L1 cell adhesion molecule (L1CAM) is overexpressed in various solid tumors, and its overexpression is linked to increased invasion, metastasis, angiogenesis, cancer stemness, and therapy resistance. However, the mechanisms of L1CAM-mediated carcinogenesis and radioresistance, particularly in high-grade serous ovarian carcinoma (HGSOC), the most common and lethal type of ovarian cancer, remain insufficiently understood. Anti-L1CAM radioimmunotherapy (RIT) using the radioisotopes Terbium-161 (Tb-161) and Lutetium-177 (Lu-177) has shown that Tb-161 is more cytotoxic than Lu-177, due to its distinct radioactive properties. Moreover, we identified a population of L1CAM+/CD133+ cells as cancer stem cells (CSCs) in ovarian cancer and demonstrated L1CAM's association with radioresistance. Understanding L1CAM-regulated downstream signaling and cellular responses to anti-L1CAM RIT with Tb-161, compared to Lu-177, is now critical. To address this, we established CRISPR-Cas9-mediated L1CAM knock-out (ΔL1CAM) in human ovarian cancer cells (OVCAR8) alongside a control cell line with a knockout of the nonessential gene AAVS1 (ΔAAVS1). In this study, quantitative phosphoproteomics, coupled with matching proteomics, revealed (i) L1CAM-dependent signaling pathways and biological processes by comparing ΔL1CAM with wild-type cells, and (ii) cellular responses to anti-L1CAM RIT with Tb-161 and Lu-177 in L1CAM-expressing ovarian cancer cells.
HostingRepository	PRIDE
AnnounceDate	2025-06-02
AnnouncementXML	Submission_2025-06-01_16:10:54.866.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michal Grzmil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-03 10:35:49	ID requested
⏵ 1	2025-06-01 16:10:55	announced

10.3390/ijms26104585;

Todorov TZ, Coelho R, Jacob F, Heinzelmann-Schwarz V, Schibli R, B, é, h, é M, Gr, ü, nberg J, Grzmil M, Phosphoproteomics Reveals L1CAM-Associated Signaling Networks in High-Grade Serous Ovarian Carcinoma: Implications for Radioresistance and Tumorigenesis. Int J Mol Sci, 26(10):(2025) [pubmed]

submitter keyword: TMT,Human ovarian cancer, L1CAM, phosphoproteomics, radioimmunotherapy

Michal Grzmil
contact affiliation	Paul Scherrer Institute, Center for Radiopharmaceutica Sciences, 5232 Villigen PSI, Switzerland
contact email	michal.grzmil@psi.ch
lab head
Michal Grzmil
contact affiliation	Paul Scherrer Institute Center for Radiopharmaceutical Sciences
contact email	michal.grzmil@psi.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD055521
     1. Label: PRIDE project
     2. Name: Analysis of L1CAM-regulated signaling pathways and cellular responses to anti-L1CAM radioimmunotherapy in human ovarian cancer cells