Evidence map›Paper›PMID 39138495›Full record

ArticleCell communication and signaling : CCS2024

Activity-based protein profiling and global proteome analysis reveal MASTL as a potential therapeutic target in gastric cancer.

Kyoung-Min Choi, Sung-Jin Kim, Mi-Jung Ji, Eunjung Kim, Jae-Sung Kim, Hyun-Mee Park, Jae-Young Kim

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Kyoung-Min Choi *Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea.
Sung-Jin Kim *Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea.
Mi-Jung JiAdvanced Analysis and Data Center, Korea Institute of Science and Technology (KIST), Seoul, 02456, Republic of Korea.
Eunjung KimNatural Product Informatics Center, Korea Institute of Science and Technology (KIST), Gangneung, 25451, Republic of Korea.
Jae-Sung KimDivision of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
Hyun-Mee ParkAdvanced Analysis and Data Center, Korea Institute of Science and Technology (KIST), Seoul, 02456, Republic of Korea.
Jae-Young KimGraduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea. jaeyoungkim@cnu.ac.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGastric cancer (GC) is a prevalent malignancy with limited therapeutic options for advanced stages. This study aimed to identify novel therapeutic targets for GC by profiling HSP90 client kinases.

methodsWe used mass spectrometry-based activity-based protein profiling (ABPP) with a desthiobiotin-ATP probe, combined with sensitivity analysis of HSP90 inhibitors, to profile kinases in a panel of GC cell lines. We identified kinases regulated by HSP90 in inhibitor-sensitive cells and investigated the impact of MASTL knockdown on GC cell behavior. Global proteomic analysis following MASTL knockdown was performed, and bioinformatics tools were used to analyze the resulting data.

resultsFour kinases-MASTL, STK11, CHEK1, and MET-were identified as HSP90-regulated in HSP90 inhibitor-sensitive cells. Among these, microtubule-associated serine/threonine kinase-like (MASTL) was upregulated in GC and associated with poor prognosis. MASTL knockdown decreased migration, invasion, and proliferation of GC cells. Global proteomic profiling following MASTL knockdown revealed NEDD4-1 as a potential downstream mediator of MASTL in GC progression. NEDD4-1 was also upregulated in GC and associated with poor prognosis. Similar to MASTL inhibition, NEDD4-1 knockdown suppressed migration, invasion, and proliferation of GC cells.

conclusionsOur multi-proteomic analyses suggest that targeting MASTL could be a promising therapy for advanced gastric cancer, potentially through the reduction of tumor-promoting proteins including NEDD4-1. This study enhances our understanding of kinase signaling pathways in GC and provides new insights for potential treatment strategies.

Indexed as

Cell ProliferationProtein Serine-Threonine KinasesProteomeProteomicsStomach NeoplasmsCell Line, TumorCell MovementGene Expression Regulation, NeoplasticHSP90 Heat-Shock ProteinsHumansMicrotubule-Associated ProteinsMolecular Targeted TherapyNedd4 Ubiquitin Protein LigasesHSP90 Heat-Shock ProteinsMASTL protein, humanMicrotubule-Associated ProteinsNedd4 Ubiquitin Protein LigasesProtein Serine-Threonine KinasesProteomeActivity-based Protein ProfilingGastric cancerMASTLNEDD4-1Proteomics

Identifiers

PMID39138495
PMCPMC11323684

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.