Choi, Kyoung-Min Kim, Sung-Jin Ji, Mi-Jung Kim, Eunjung Kim, Jae-Sung Park, Hyun-Mee Kim, Jae-Young 2024-08-23T09:00:21Z 2024-08-23T09:00:21Z 2024-08-22 2024-08 1478-811X https://pubs.kist.re.kr/handle/201004/150483 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. English BioMed Central Activity-based protein profiling and global proteome analysis reveal MASTL as a potential therapeutic target in gastric cancer Article 10.1186/s12964-024-01783-8 1 Cell Communication and Signaling, v.22, no.1 Cell Communication and Signaling 22 1 Y scie scopus 001290250600002 2-s2.0-85201253544 Cell Biology Cell Biology Article MATRIX METALLOPROTEINASES IMMUNOLOGICAL ROLES ANTITUMOR-ACTIVITY HSP90 INHIBITOR ANLN ANILLIN KINASE CHK1 OVEREXPRESSION INTERROGATION Gastric cancer Activity-based Protein Profiling Proteomics MASTL NEDD4-1