An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization
Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin β1-containing, filopodium-like protrusions (FLPs), which enable them to interact productively with the surrounding extracellular matrix; this process governs the initia...
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| 格式: | 文件 |
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Elsevier
2018
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| 在线阅读: | http://hdl.handle.net/1721.1/116945 https://orcid.org/0000-0002-0895-3557 |
| _version_ | 1826188121201442816 |
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| author | Shibue, Tsukasa Brooks, Mary W. Weinberg, Robert A |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Shibue, Tsukasa Brooks, Mary W. Weinberg, Robert A |
| author_sort | Shibue, Tsukasa |
| collection | MIT |
| description | Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin β1-containing, filopodium-like protrusions (FLPs), which enable them to interact productively with the surrounding extracellular matrix; this process governs the initial proliferation of these cancer cells. Here, we identify the signaling pathway governing FLP lifetime, which involves integrin-linked kinase (ILK) and β-parvin, two integrin:actin-bridging proteins that block cofilin-mediated actin-filament severing. Notably, the combined actions of Rif/mDia2 and ILK/β-parvin/cofilin pathways on FLPs are required not only for metastatic outgrowth but also for primary tumor formation following experimental implantation. This provides one mechanistic explanation for how the epithelial-mesenchymal transition (EMT) program imparts tumor-initiating powers to carcinoma cells, since it enhances FLP formation through the activation of ILK/β-parvin/cofilin pathway. |
| first_indexed | 2024-09-23T07:54:55Z |
| format | Article |
| id | mit-1721.1/116945 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T07:54:55Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1169452022-09-30T00:59:21Z An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization Shibue, Tsukasa Brooks, Mary W. Weinberg, Robert A Massachusetts Institute of Technology. Department of Biology Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology) Shibue, Tsukasa Brooks, Mary W. Weinberg, Robert A Recently extravasated metastatic cancer cells use the Rif/mDia2 actin-nucleating/polymerizing machinery in order to extend integrin β1-containing, filopodium-like protrusions (FLPs), which enable them to interact productively with the surrounding extracellular matrix; this process governs the initial proliferation of these cancer cells. Here, we identify the signaling pathway governing FLP lifetime, which involves integrin-linked kinase (ILK) and β-parvin, two integrin:actin-bridging proteins that block cofilin-mediated actin-filament severing. Notably, the combined actions of Rif/mDia2 and ILK/β-parvin/cofilin pathways on FLPs are required not only for metastatic outgrowth but also for primary tumor formation following experimental implantation. This provides one mechanistic explanation for how the epithelial-mesenchymal transition (EMT) program imparts tumor-initiating powers to carcinoma cells, since it enhances FLP formation through the activation of ILK/β-parvin/cofilin pathway. National Institutes of Health (U.S.) (Grant P01 CA080111) National Institutes of Health (U.S.) (Grant U54-CA163109) 2018-07-12T18:22:36Z 2018-07-12T18:22:36Z 2013-09 2013-04 2018-07-12T17:24:38Z Article http://purl.org/eprint/type/JournalArticle 1535-6108 http://hdl.handle.net/1721.1/116945 Shibue, Tsukasa et al. “An Integrin-Linked Machinery of Cytoskeletal Regulation That Enables Experimental Tumor Initiation and Metastatic Colonization.” Cancer Cell 24, 4 (October 2013): 481–498 © 2013 Elsevier Inc https://orcid.org/0000-0002-0895-3557 http://dx.doi.org/10.1016/J.CCR.2013.08.012 Cancer Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Shibue, Tsukasa Brooks, Mary W. Weinberg, Robert A An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title | An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title_full | An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title_fullStr | An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title_full_unstemmed | An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title_short | An Integrin-Linked Machinery of Cytoskeletal Regulation that Enables Experimental Tumor Initiation and Metastatic Colonization |
| title_sort | integrin linked machinery of cytoskeletal regulation that enables experimental tumor initiation and metastatic colonization |
| url | http://hdl.handle.net/1721.1/116945 https://orcid.org/0000-0002-0895-3557 |
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