Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer

Cell Communication and Signaling : CCS
Jinrui ZhangHan Liu

Abstract

ErbB2 overexpression identifies a subset of breast cancer as ErbB2-positive and is frequently associated with poor clinical outcomes. As a membrane-embedded receptor tyrosine kinase, cell surface levels of ErbB2 are regulated dynamically by membrane physical properties. The present study aims to investigate the influence of membrane cholesterol contents on ErbB2 status and cellular responses to its tyrosine kinase inhibitors. The cholesterol abundance was examined in ErbB2-positive breast cancer cells using filipin staining. Cellular ErbB2 localizations were investigated by immunofluorescence with altered membrane cholesterol contents. The inhibitory effects of the cholesterol-lowering drug lovastatin were assessed using cell proliferation, apoptosis, immunoblotting and immunofluorescence assays. The synergistic effects of lovastatin with the ErbB2 inhibitor lapatinib were evaluated using an ErbB2-positive breast cancer xenograft mouse model. Membrane cholesterol contents positively correlated with cell surface distribution of ErbB2 through increasing the rigidity and decreasing the fluidity of cell membranes. Reduction in cholesterol abundance assisted the internalization and degradation of ErbB2. The cholesterol-lowering drug...Continue Reading

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Citations

Jul 28, 2020·Frontiers in Immunology·Sibel KaraAnja Lux
Dec 28, 2019·Cell Communication and Signaling : CCS·Magdalena Banach-OrłowskaMarta Miączyńska
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Jun 11, 2021·Frontiers in Oncology·Isabella GiacominiVeronica Cocetta
Nov 12, 2020·ACS Infectious Diseases·Dana Logviniuk, Micha Fridman

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Methods Mentioned

BETA
protein assays
xenograft
xenografts
fluorescence microscopy

Software Mentioned

Image Studio
FlowJo
GraphPad Prism

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