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Interaction between CD147 and P-Glycoprotein and Their Regulation by Ubiquitination in Breast Cancer Cells
by
Tang, Feng
, Li, Hai-Xia
, Wang, Wen-Juan
, Xu, Zu-De
, Liu, Xiu-Ping
, Cao, Xi-Xi
, Yang, Jin-Ming
, Chen, Qi
, Li, Qing-Quan
, Xu, Jing-Da
in
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
/ ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
/ Basigin - genetics
/ Basigin - metabolism
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cell Line, Tumor
/ Cellular biology
/ Chemotherapy
/ Collagenases - genetics
/ Collagenases - metabolism
/ Experimental Chemotherapy
/ Gene Expression Regulation, Neoplastic
/ Glycoproteins
/ Humans
/ Medical research
/ Paclitaxel - pharmacology
/ Proteasome Endopeptidase Complex - metabolism
/ Protein Binding
/ RNA, Messenger - genetics
/ RNA, Small Interfering - genetics
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
2008
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Interaction between CD147 and P-Glycoprotein and Their Regulation by Ubiquitination in Breast Cancer Cells
by
Tang, Feng
, Li, Hai-Xia
, Wang, Wen-Juan
, Xu, Zu-De
, Liu, Xiu-Ping
, Cao, Xi-Xi
, Yang, Jin-Ming
, Chen, Qi
, Li, Qing-Quan
, Xu, Jing-Da
in
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
/ ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
/ Basigin - genetics
/ Basigin - metabolism
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cell Line, Tumor
/ Cellular biology
/ Chemotherapy
/ Collagenases - genetics
/ Collagenases - metabolism
/ Experimental Chemotherapy
/ Gene Expression Regulation, Neoplastic
/ Glycoproteins
/ Humans
/ Medical research
/ Paclitaxel - pharmacology
/ Proteasome Endopeptidase Complex - metabolism
/ Protein Binding
/ RNA, Messenger - genetics
/ RNA, Small Interfering - genetics
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
2008
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Interaction between CD147 and P-Glycoprotein and Their Regulation by Ubiquitination in Breast Cancer Cells
by
Tang, Feng
, Li, Hai-Xia
, Wang, Wen-Juan
, Xu, Zu-De
, Liu, Xiu-Ping
, Cao, Xi-Xi
, Yang, Jin-Ming
, Chen, Qi
, Li, Qing-Quan
, Xu, Jing-Da
in
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
/ ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
/ Basigin - genetics
/ Basigin - metabolism
/ Breast cancer
/ Breast Neoplasms - genetics
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cell Line, Tumor
/ Cellular biology
/ Chemotherapy
/ Collagenases - genetics
/ Collagenases - metabolism
/ Experimental Chemotherapy
/ Gene Expression Regulation, Neoplastic
/ Glycoproteins
/ Humans
/ Medical research
/ Paclitaxel - pharmacology
/ Proteasome Endopeptidase Complex - metabolism
/ Protein Binding
/ RNA, Messenger - genetics
/ RNA, Small Interfering - genetics
/ Ubiquitin Thiolesterase - genetics
/ Ubiquitin Thiolesterase - metabolism
/ Ubiquitination
2008
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Interaction between CD147 and P-Glycoprotein and Their Regulation by Ubiquitination in Breast Cancer Cells
Journal Article
Interaction between CD147 and P-Glycoprotein and Their Regulation by Ubiquitination in Breast Cancer Cells
2008
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Overview
Background: Multidrug-resistant cancer cells overexpressing P-glycoprotein (P-gp) display variations in invasive and metastatic ability through the upregulation of the extracellular matrix metalloproteinase (MMP) inducer (CD147). However, the direct linkage between these two proteins is still unclear. Methods: We used immunoprecipitation, immunofluorescence analysis, migration and invasion assays, drug sensitivity assay and Western blot to measure the physical and functional interaction between P-gp and CD147. Then we transfected vectors carrying ubiquitin C-terminal hydrolase L1 (UCH-L1) or UCH-L1 siRNA into MCF7 and MCF7/Adr cells, respectively, and investigated the role of UCH-L1 in the regulation of the expression and degradation of P-gp, CD147 and MMP-1, MMP-2, and MMP-9 by quantitative real-time polymerase chain reaction, Western blot and immunoprecipitation. Results: In this paper, we showed that P-gp and CD147 interacted with each other, and that the ubiquitin-proteasome pathway played an important role in the turnover of them. In addition, we found that inhibition of N-glycosylation increased the ubiquitination and degradation of P-gp and CD147, and affected their function. UCH-L1 not only regulated the expression of P-gp, CD147 and MMP-1, MMP-2, and MMP-9, but also the ubiquitination and degradation of P-gp and CD147 in breast cancer cells. Conclusion: Our results demonstrate a mechanism underlying the linkage between multidrug resistance and tumor metastasis, and suggest for the first time that modulating the ubiquitination of P-gp and CD147 might be a novel method for tumor therapy.
Publisher
S. Karger AG
Subject
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
/ ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Proteasome Endopeptidase Complex - metabolism
/ RNA, Small Interfering - genetics
/ Ubiquitin Thiolesterase - genetics
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