Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus
The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focus...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1100938/full |
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| author | Takouhie Mgrditchian Joshua Brown-Clay Céline Hoffmann Tanja Müller Liza Filali Elena Ockfen Xianqing Mao Flora Moreau Carla Pou Casellas Tony Kaoma Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Clément Thomas |
| author_facet | Takouhie Mgrditchian Joshua Brown-Clay Céline Hoffmann Tanja Müller Liza Filali Elena Ockfen Xianqing Mao Flora Moreau Carla Pou Casellas Tony Kaoma Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Clément Thomas |
| author_sort | Takouhie Mgrditchian |
| collection | DOAJ |
| description | The actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells. We found that F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13. Our data suggest that CRP2 and SRF cooperate to modulate of MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant metastasis-free survival in breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in breast cancer cells. |
| first_indexed | 2024-03-13T10:54:40Z |
| format | Article |
| id | doaj.art-c2b8619594984cbea893d4b0fc76ae51 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T10:54:40Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c2b8619594984cbea893d4b0fc76ae512023-05-17T05:30:55ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-05-011110.3389/fcell.2023.11009381100938Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleusTakouhie Mgrditchian0Joshua Brown-Clay1Céline Hoffmann2Tanja Müller3Liza Filali4Elena Ockfen5Xianqing Mao6Flora Moreau7Carla Pou Casellas8Tony Kaoma9Michel Mittelbronn10Michel Mittelbronn11Michel Mittelbronn12Michel Mittelbronn13Michel Mittelbronn14Michel Mittelbronn15Clément Thomas16Department of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Luxembourg Centre of Neuropathology, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgBioinformatics Platform, Luxembourg, LuxembourgDepartment of Cancer Research, Luxembourg Centre of Neuropathology, Luxembourg Institute of Health, Luxembourg, LuxembourgLuxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-surAlzette, LuxembourgFaculty of Science, Technology and Medicine (FSTM), University of Luxembourg, Esch-surAlzette, LuxembourgDepartment of Life Science and Medicine (DLSM), University of Luxembourg, Esch-surAlzette, LuxembourgNational Center of Pathology (NCP), Laboratoire National de Santé (LNS), Dudelange, LuxembourgLuxembourg Center of Neuropathology (LCNP), Dudelange, LuxembourgDepartment of Cancer Research, Cytoskeleton and Cancer Progression, Luxembourg Institute of Health, Luxembourg, LuxembourgThe actin cytoskeleton plays a critical role in cancer cell invasion and metastasis; however, the coordination of its multiple functions remains unclear. Actin dynamics in the cytoplasm control the formation of invadopodia, which are membrane protrusions that facilitate cancer cell invasion by focusing the secretion of extracellular matrix-degrading enzymes, including matrix metalloproteinases (MMPs). In this study, we investigated the nuclear role of cysteine-rich protein 2 (CRP2), a two LIM domain-containing F-actin-binding protein that we previously identified as a cytoskeletal component of invadopodia, in breast cancer cells. We found that F-actin depolymerization stimulates the translocation of CRP2 into the nucleus, resulting in an increase in the transcript levels of pro-invasive and pro-metastatic genes, including several members of the MMP gene family. We demonstrate that in the nucleus, CRP2 interacts with the transcription factor serum response factor (SRF), which is crucial for the expression of MMP-9 and MMP-13. Our data suggest that CRP2 and SRF cooperate to modulate of MMP expression levels. Furthermore, Kaplan-Meier analysis revealed a significant association between high-level expression of SRF and shorter overall survival and distant metastasis-free survival in breast cancer patients with a high CRP2 expression profile. Our findings suggest a model in which CRP2 mediates the coordination of cytoplasmic and nuclear processes driven by actin dynamics, ultimately resulting in the induction of invasive and metastatic behavior in breast cancer cells.https://www.frontiersin.org/articles/10.3389/fcell.2023.1100938/fullActin cytoskeletonbreast cancercysteine-rich protein 2 (CRP2)gene transcriptionmatrix metalloproteinases (MMPs)metastasis |
| spellingShingle | Takouhie Mgrditchian Joshua Brown-Clay Céline Hoffmann Tanja Müller Liza Filali Elena Ockfen Xianqing Mao Flora Moreau Carla Pou Casellas Tony Kaoma Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Michel Mittelbronn Clément Thomas Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus Frontiers in Cell and Developmental Biology Actin cytoskeleton breast cancer cysteine-rich protein 2 (CRP2) gene transcription matrix metalloproteinases (MMPs) metastasis |
| title | Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus |
| title_full | Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus |
| title_fullStr | Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus |
| title_full_unstemmed | Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus |
| title_short | Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus |
| title_sort | actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine rich protein 2 to the nucleus |
| topic | Actin cytoskeleton breast cancer cysteine-rich protein 2 (CRP2) gene transcription matrix metalloproteinases (MMPs) metastasis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1100938/full |
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