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HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis
Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Her...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031283/ https://www.ncbi.nlm.nih.gov/pubmed/36970214 http://dx.doi.org/10.1016/j.apsb.2022.11.025 |
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author | Zhang, Lu Zhou, Xiaolei Liu, Bowen Shi, Xuhe Li, Xianmeng Xu, Feifei Fu, Xueli Wang, Xue Ye, Kai Jin, Tianzhi Sun, Huimin Li, Qianqian Zhang, Weiying Ye, Lihong |
author_facet | Zhang, Lu Zhou, Xiaolei Liu, Bowen Shi, Xuhe Li, Xianmeng Xu, Feifei Fu, Xueli Wang, Xue Ye, Kai Jin, Tianzhi Sun, Huimin Li, Qianqian Zhang, Weiying Ye, Lihong |
author_sort | Zhang, Lu |
collection | PubMed |
description | Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer. |
format | Online Article Text |
id | pubmed-10031283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100312832023-03-23 HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis Zhang, Lu Zhou, Xiaolei Liu, Bowen Shi, Xuhe Li, Xianmeng Xu, Feifei Fu, Xueli Wang, Xue Ye, Kai Jin, Tianzhi Sun, Huimin Li, Qianqian Zhang, Weiying Ye, Lihong Acta Pharm Sin B Original Article Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer. Elsevier 2023-03 2022-11-25 /pmc/articles/PMC10031283/ /pubmed/36970214 http://dx.doi.org/10.1016/j.apsb.2022.11.025 Text en © 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Zhang, Lu Zhou, Xiaolei Liu, Bowen Shi, Xuhe Li, Xianmeng Xu, Feifei Fu, Xueli Wang, Xue Ye, Kai Jin, Tianzhi Sun, Huimin Li, Qianqian Zhang, Weiying Ye, Lihong HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title | HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title_full | HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title_fullStr | HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title_full_unstemmed | HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title_short | HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis |
title_sort | hbxip blocks myosin-iia assembly by phosphorylating and interacting with nmhc-iia in breast cancer metastasis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031283/ https://www.ncbi.nlm.nih.gov/pubmed/36970214 http://dx.doi.org/10.1016/j.apsb.2022.11.025 |
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