ArticleProteome science2023
Analysis of differential membrane proteins related to matrix stiffness-mediated metformin resistance in hepatocellular carcinoma cells.
Article in Proteome science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- MYH9: Structure, functions, and therapeutic implications in cancer and genetic disorders.Genes & diseases · 2026Review
- Deciphering Stiffness-Driven Changes in Colorectal Cancer by Proteomics.Molecular & cellular proteomics : MCP · 2026Article
- Profiling the Complexity of Resistance Factors in Cancer Cells Towards Berberine and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Exploring the Proteomic Landscape of Cochlear Implant Trauma: An iTRAQ-Based Quantitative Analysis Utilizing an Ex Vivo Model.Journal of clinical medicine · 2025Article
- Exploring the nexus between MYH9 and tumors: novel insights and new therapeutic opportunities.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundOur previous work shows that increased matrix stiffness not only alters malignant characteristics of hepatocellular carcinoma (HCC) cells, but also attenuates metformin efficacy in treating HCC cells. Here, we identified differential membrane proteins related to matrix stiffness-mediated metformin resistance for better understand therapeutic resistance of metformin in HCC.
methodsDifferential membrane proteins in HCC cells grown on different stiffness substrates before and after metformin intervention were screened and identified using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with the liquid chromatography-tandem mass spectrometry (LC-MS/MS), then bioinformatic analysis were applied to determine candidate membrane protein and their possible signaling pathway.
resultsA total of 5159 proteins were identified and 354 differential membrane proteins and membrane associated proteins, which might be associated with matrix stiffness-mediated metformin resistance were discovered. Then 94 candidate membrane proteins including 21 up-regulated protein molecules and 73 down-regulated protein molecules were further obtained. Some of them such as Annexin A2 (ANXA2), Filamin-A (FLNA), Moesin (MSN), Myosin-9 (MYH9), Elongation factor 2 (eEF2), and Tax1 binding Protein 3 (TAX1BP3) were selected for further validation. Their expressions were all downregulated in HCC cells grown on different stiffness substrates after metformin intervention. More importantly, the degree of decrease was obviously weakened on the higher stiffness substrate compared with that on the lower stiffness substrate, indicating that these candidate membrane proteins might contribute to matrix stiffness-mediated metformin resistance in HCC.
conclusionsThere was an obvious change in membrane proteins in matrix stiffness-mediated metformin resistance in HCC cells. Six candidate membrane proteins may reflect the response of HCC cells under high stiffness stimulation to metformin intervention, which deserve to be investigated in the future.
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