Dataset Information

Quantitative proteomic analysis of MCF10A cells with PTEN knockout reveals the regulation of EphA2 expression by PTEN

ABSTRACT: 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Xinyan Wu

LAB HEAD: Xinyan Wu

PROVIDER: PXD057520 | Pride | 2025-12-15

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Hongming_PTEN_KO_TMT9plex_bRPLC_F01.raw	Raw
	Hongming_PTEN_KO_TMT9plex_bRPLC_F02.raw	Raw
	Hongming_PTEN_KO_TMT9plex_bRPLC_F03.raw	Raw
	Hongming_PTEN_KO_TMT9plex_bRPLC_F04.raw	Raw
	Hongming_PTEN_KO_TMT9plex_bRPLC_F05.raw	Raw

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Publications

Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition.

Wang Qiong Q Kong Xiangyi X Song Hongming H Wang Li L Li Lingrui L Hou Xiaonan X Renuse Santosh S Zahari Muhammad Saddiq MS Cheng Ran R Khan Md Kamrul Hasan MKH Wang Jidong J Mangalaparthi Kiran K Fang Lin L Lotan Tamara Levin TL Park Ben Ho BH Weroha S John SJ Zhou Huaijun H Pandey Akhilesh A Wu Xinyan X

Molecular & cellular proteomics : MCP 20251021 12

Loss of the tumor suppressor phosphatase and tensin homolog (PTEN) is frequently observed in various cancers and promotes tumorigenesis by activating the PI3K-AKT pathway. However, the effectiveness of therapies targeting this pathway is limited by complex signaling crosstalk and compensatory mechanisms. Here, we employed quantitative proteomic and phosphoproteomic analyses using MCF10A PTEN KO models to comprehensively map the signaling alterations induced by PTEN loss. Our analyses revealed th ...[more]

PMID: 41130297

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