PXD057520

PXD057520 is an original dataset announced via ProteomeXchange.

Title	Quantitative proteomic analysis of MCF10A cells with PTEN knockout reveals the regulation of EphA2 expression by PTEN
Description	PTEN, a well-known tumor suppressor, negatively regulates the PI3K-AKT signaling pathway. Its loss is prevalent across various cancer types and leads to significant changes in cellular signaling networks. In this study, we investigate the effects of PTEN loss on both canonical PI3K-AKT and noncanonical tyrosine kinase pathways in MCF10A PTEN knockout (KO) cells. Through quantitative proteomics and phosphoproteomics, we identified substantial changes in protein and phosphorylation profiles, including key signaling regulators such as EphA2, Src, and MEK-ERK1/2. Our findings reveal that PTEN loss not only activates PI3K-AKT signaling but also elevates tyrosine kinase signaling, with Src kinase playing a crucial role in upregulating EphA2, an RTK implicated in tumor progression. Interestingly, inhibition of AKT alone did not consistently reduce EphA2 levels, highlighting an AKT-independent mechanism of EphA2 regulation via Src in PTEN-deficient cells. We demonstrated that combined targeting of AKT and Src pathways using Capivasertib (AKT inhibitor) and Dasatinib (Src inhibitor) significantly suppressed proliferation and induced apoptosis in PTEN-deficient breast and endometrial cancer cell lines, with notable synergy observed in patient-derived xenograft (PDX) models. These results suggest that dual inhibition of AKT and Src could provide a promising therapeutic approach for PTEN-deficient cancers, addressing resistance limitations associated with AKT inhibition alone and improving therapeutic efficacy. This study underscores the complex regulatory mechanisms involving PTEN and highlights new possibilities for targeted combination therapies in cancers with PTEN loss.
HostingRepository	PRIDE
AnnounceDate	2025-12-15
AnnouncementXML	Submission_2025-12-14_18:51:04.044.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xinyan Wu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-05 00:45:42	ID requested
⏵ 1	2025-12-14 18:51:05	announced

10.1016/j.mcpro.2025.101316;

Wang Q, Kong X, Song H, Wang L, Li L, Hou X, Renuse S, Zahari MS, Cheng R, Khan MKH, Wang J, Mangalaparthi K, Fang L, Lotan TL, Park BH, Weroha SJ, Zhou H, Pandey A, Wu X, Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition. Mol Cell Proteomics, 24(12):101316(2025) [pubmed]

submitter keyword: Human breast epithelial cells

Xinyan Wu
contact affiliation	Mayo Clinic
contact email	wu.xinyan@mayo.edu
lab head
Xinyan Wu
contact affiliation	Mayo Clinic
contact email	wu.xinyan@mayo.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD057520
     1. Label: PRIDE project
     2. Name: Quantitative proteomic analysis of MCF10A cells with PTEN knockout reveals the regulation of EphA2 expression by PTEN