ArticleOncoTargets and therapy2020
PHLPP Sensitizes Multiple Myeloma Cells to Bortezomib Through Regulating LAMP2.
Article in OncoTargets and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- PHLPP and LAMP2 predict favorable treatment response and survival in multiple myeloma patients who receive induction treatment with bortezomib.Irish journal of medical science · 2025Article
- Reduced PHLPP Expression Leads to EGFR-TKI Resistance in Lung Cancer by Activating PI3K-AKT and MAPK-ERK Dual Signaling.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTreatment of bortezomib (BTZ) improves the clinical outcomes of patients with multiple myeloma (MM). However, primary resistance and acquired resistance to BTZ frequently develop in patients with MM. PH domain leucine-rich repeat protein phosphatase (PHLPP) plays an important role in chemoresistance in a number of cancers. However, the role of PHLPP on MM remains unclear. In this study, we investigated the role of PHLPP in BTZ-resistant MM cells.
methodsBrdU assays, immunoprecipitation, flow cytometry analyses, and immunofluorescence assays were performed.
resultsPHLPP and lysosome-associated membrane protein 2 (LAMP2) levels were downregulated in BTZ-resistant MM cells compared with BTZ-sensitive MM cells, accompanied by inactivation of autophagy pathway evaluated by a reduction in Beclin1, Atg5 and LC3B and increase in p62. Gain- and loss-of-function experiments revealed that PHLPP partially re-sensitized MM cells to BTZ. In addition, PHLPP overexpression increased whereas PHLPP knockdown reduced LAMP2 expression, subsequently regulating the autophagy pathway in MM cells. Further findings demonstrated that LAMP2 knockdown reversed PHLPP-mediated cell apoptosis and autophagy activation in MM cells.
conclusionThis study demonstrated that PHLPP is a potential strategy for overcoming BTZ resistance in patients with MM.
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