PXD058276-1

PXD058276 is an original dataset announced via ProteomeXchange.

Title	Effect of the Src inhibitor peptide TAT-Cx43266-283 in lung cancer brain metastasis models.
Description	Background: TAT-Cx43266-283 is a novel inhibitor of Src, which has shown important antitumor effects in preclinical models of glioblastoma. Because Src plays a pivotal role in several tumors, including lung cancer and brain metastasis, in this study we investigated the effect of TAT-Cx43266-283 in lung cancer brain metastasis, an unmet clinical need. Methods: Cancer Stem Cells (CSCs) from the murine lung cancer cell line LLC, named LLC-CSCs, were isolated and used to study the effect of TAT-Cx43266-283 in vitro and to develop an in vivo model of lung cancer brain metastasis. Thus, in vivo models were carried out performing an intracranial implantation of LLC-CSCs in immunocompetent mice and the impact of TAT-Cx43266-283 in these models was assessed. A phosphoproteomic analysis was employed to identify signaling pathways affected by TAT-Cx43266-283, and the most prominent targets were validated by immunofluorescence or Western Blot. Results: We found that TAT-Cx43266-283 significantly reduced LLC-CSCs viability and increased the survival of immunocompetent mice bearing lung cancer derived-brain metastatic tumors. Phosphoproteomic analysis identified ERK as a key effector of TAT-Cx43266-283 treatment in the LLC-CSC-derived brain metastasis model. TAT-Cx43266-283 also induced apoptosis of tumoral cells and disrupted the cytoskeleton and vascularization of the tumor tissue in this preclinical lung cancer brain metastasis model. Conclusions: Our results suggest that TAT-Cx43266-283 is a promising antitumoral drug for lung cancer brain metastasis treatment. We identified the inhibition of ERK as an important effector, together with the inhibition of Src, in the antitumoral effect of TAT-Cx43266-283 in lung cancer brain metastasis. All this together, places TAT-Cx43266-283 one step forward into its journey to its therapeutic implementation.
HostingRepository	PRIDE
AnnounceDate	2026-03-02
AnnouncementXML	Submission_2026-03-01_16:31:08.714.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058276
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Vinothini Rajeeve
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-26 03:10:18	ID requested
⏵ 1	2026-03-01 16:31:09	announced

Cerver, ó, -Garc, í, a P, Jim, é, nez-Madrona E, Á, lvarez-V, á, zquez A, Flores-Hern, á, ndez R, Garc, í, a-Vicente L, Garc, í, a-Guerrero L, Alonso-Amador JJ, Gonz, á, lez-S, á, nchez R, Ollauri-Ib, á, ñ, ez C, Paniagua-Sancho M, Talaver, ó, n R, Rodrigues-Teixeira T, Mart, í, n-Guerrero SM, Casado P, Rajeeve V, Shields T, Hijazi M, Cutillas PR, Jara, í, z-Rodr, í, guez M, Tabernero A, improves survival in an intracranial murine model of lung cancer brain metastasis. Neurooncol Adv, 8(1):vdag001(2026) [pubmed]

10.1093/noajnl/vdag001;

10.6019/PXD058276;

submitter keyword: cancer stem cells,metastasis, Src, tumor, phosphoproteomics

Pedro Rodriguez Cutillas
contact affiliation	Barts Cancer Institute, Queen Mary University of London
contact email	p.cutillas@qmul.ac.uk
lab head
Vinothini Rajeeve
contact affiliation	Centre for Haemato Oncology
contact email	v.rajeeve@qmul.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058276
     1. Label: PRIDE project
     2. Name: Effect of the Src inhibitor peptide TAT-Cx43266-283 in lung cancer brain metastasis models.