Zhang, Y., Zhang, J., Li, Q., Wu, Y., Wang, D., Xu, L., Zhang, Y., Wang, S., Wang, T., Liu, F., Zaky, M. Y., Hou, S., Liu, S., Zou, K., Lei, H., Zou, L., & Liu, H. (2019). Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer. Cell Communication and Signaling, 17(1), 文章 15. https://doi.org/10.1186/s12964-019-0328-4
Zhang, Yingqiu ; Zhang, Jinrui ; Li, Qiong 等. / Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer. 在: Cell Communication and Signaling. 2019 ; 卷 17, 号码 1.
@article{8f7801f080674f178c1cb076e50c6231,
title = "Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer",
abstract = "Background: 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. Methods: 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. Results: 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 lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion: The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.",
keywords = "Breast cancer, Cholesterol, ErbB2, Lovastatin, Membrane fluidity, Membrane rigidity",
author = "Yingqiu Zhang and Jinrui Zhang and Qiong Li and Yueguang Wu and Duchuang Wang and Lu Xu and Yang Zhang and Shanshan Wang and Taishu Wang and Fang Liu and Zaky, {Mohamed Y.} and Shuai Hou and Shuyan Liu and Kun Zou and Haixin Lei and Lijuan Zou and Han Liu",
note = "Publisher Copyright: {\textcopyright} 2019 The Author(s).",
year = "2019",
month = feb,
day = "20",
doi = "10.1186/s12964-019-0328-4",
language = "English",
volume = "17",
journal = "Cell Communication and Signaling",
issn = "1478-811X",
publisher = "Signal Transduction Society",
number = "1",
}
Zhang, Y, Zhang, J, Li, Q, Wu, Y, Wang, D, Xu, L, Zhang, Y, Wang, S, Wang, T, Liu, F, Zaky, MY, Hou, S, Liu, S, Zou, K, Lei, H, Zou, L & Liu, H 2019, 'Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer', Cell Communication and Signaling, 卷 17, 号码 1, 15. https://doi.org/10.1186/s12964-019-0328-4
Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer. / Zhang, Yingqiu; Zhang, Jinrui; Li, Qiong 等.
在:
Cell Communication and Signaling, 卷 17, 号码 1, 15, 20.02.2019.
科研成果: 期刊稿件 › 文章 › 同行评审
TY - JOUR
T1 - Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer
AU - Zhang, Yingqiu
AU - Zhang, Jinrui
AU - Li, Qiong
AU - Wu, Yueguang
AU - Wang, Duchuang
AU - Xu, Lu
AU - Zhang, Yang
AU - Wang, Shanshan
AU - Wang, Taishu
AU - Liu, Fang
AU - Zaky, Mohamed Y.
AU - Hou, Shuai
AU - Liu, Shuyan
AU - Zou, Kun
AU - Lei, Haixin
AU - Zou, Lijuan
AU - Liu, Han
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/2/20
Y1 - 2019/2/20
N2 - Background: 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. Methods: 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. Results: 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 lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion: The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.
AB - Background: 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. Methods: 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. Results: 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 lovastatin significantly potentiated the inhibitory effects of ErbB2 kinase inhibitors, accompanied with enhanced ErbB2 endocytosis. Lovastatin also synergized with lapatinib to strongly suppress the in vivo growth of ErbB2-positive breast cancer xenografts. Conclusion: The cell surface distribution of ErbB2 was closely regulated by membrane physical properties governed by cholesterol contents. The cholesterol-lowering medications can hence be exploited for potential combinatorial therapies with ErbB2 kinase inhibitors in the clinical treatment of ErbB2-positive breast cancer.
KW - Breast cancer
KW - Cholesterol
KW - ErbB2
KW - Lovastatin
KW - Membrane fluidity
KW - Membrane rigidity
UR - http://www.scopus.com/inward/record.url?scp=85061960129&partnerID=8YFLogxK
U2 - 10.1186/s12964-019-0328-4
DO - 10.1186/s12964-019-0328-4
M3 - Article
C2 - 30786890
AN - SCOPUS:85061960129
SN - 1478-811X
VL - 17
JO - Cell Communication and Signaling
JF - Cell Communication and Signaling
IS - 1
M1 - 15
ER -
Zhang Y, Zhang J, Li Q, Wu Y, Wang D, Xu L 等. Cholesterol content in cell membrane maintains surface levels of ErbB2 and confers a therapeutic vulnerability in ErbB2-positive breast cancer. Cell Communication and Signaling. 2019 2月 20;17(1):15. doi: 10.1186/s12964-019-0328-4
