MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients
The extracellular matrix (ECM) surrounding cancer cells becomes stiffer during tumor progression, which influences cancer cell behaviors such as invasion and proliferation through modulation of gene expression as well as remodeling of the actin cytoskeleton. In this study, we show that <i>MMP2...
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MDPI AG
2020-02-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/7/1/18 |
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| author | Wataru Sugimoto Katsuhiko Itoh Hiroaki Hirata Yoshinori Abe Takeru Torii Yasumasa Mitsui Yemima Budirahardja Nobuyuki Tanaka Keiko Kawauchi |
| author_facet | Wataru Sugimoto Katsuhiko Itoh Hiroaki Hirata Yoshinori Abe Takeru Torii Yasumasa Mitsui Yemima Budirahardja Nobuyuki Tanaka Keiko Kawauchi |
| author_sort | Wataru Sugimoto |
| collection | DOAJ |
| description | The extracellular matrix (ECM) surrounding cancer cells becomes stiffer during tumor progression, which influences cancer cell behaviors such as invasion and proliferation through modulation of gene expression as well as remodeling of the actin cytoskeleton. In this study, we show that <i>MMP24</i> encoding matrix metalloproteinase (MMP)-24 is a novel target gene of Yes-associated protein (YAP), a transcription coactivator known as a mechanotransducer. We first examined the effect of substrate stiffness on <i>MMP24</i> expression in MCF-7 human breast cancer cells and showed that the expression of <i>MMP24</i> was significantly higher in cells grown on stiff substrates than that on soft substrates. The <i>MMP24</i> expression was significantly reduced by knockdown of YAP. In contrast, the expression of constitutively active YAP increased <i>MMP24</i> promoter activity. In addition, binding of YAP to the <i>MMP24</i> promoter was confirmed by the chromatin immunoprecipitation (ChIP) assay. These results show that ECM stiffening promotes YAP activation, thereby inducing <i>MMP24</i> expression. Based on the Human Protein Atlas database, breast cancer patients with lower <i>MMP24</i> expression exhibit the worse survival rates overall. Thus, <i>MMP24</i> may negatively regulate the aggressiveness of cancer cells under the stiff ECM environment during tumor progression. |
| first_indexed | 2024-03-12T06:02:38Z |
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| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-12T06:02:38Z |
| publishDate | 2020-02-01 |
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| series | Bioengineering |
| spelling | doaj.art-3e951c9679464b00ba42ba075d2f86012023-09-03T04:00:33ZengMDPI AGBioengineering2306-53542020-02-01711810.3390/bioengineering7010018bioengineering7010018MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer PatientsWataru Sugimoto0Katsuhiko Itoh1Hiroaki Hirata2Yoshinori Abe3Takeru Torii4Yasumasa Mitsui5Yemima Budirahardja6Nobuyuki Tanaka7Keiko Kawauchi8Frontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanFrontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanMechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, JapanDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo 113-0033, JapanFrontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanFrontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanFrontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanDepartment of Molecular Oncology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo 113-0033, JapanFrontiers of Innovative Research in Science and Technology, Konan University, Kobe 650-0047, JapanThe extracellular matrix (ECM) surrounding cancer cells becomes stiffer during tumor progression, which influences cancer cell behaviors such as invasion and proliferation through modulation of gene expression as well as remodeling of the actin cytoskeleton. In this study, we show that <i>MMP24</i> encoding matrix metalloproteinase (MMP)-24 is a novel target gene of Yes-associated protein (YAP), a transcription coactivator known as a mechanotransducer. We first examined the effect of substrate stiffness on <i>MMP24</i> expression in MCF-7 human breast cancer cells and showed that the expression of <i>MMP24</i> was significantly higher in cells grown on stiff substrates than that on soft substrates. The <i>MMP24</i> expression was significantly reduced by knockdown of YAP. In contrast, the expression of constitutively active YAP increased <i>MMP24</i> promoter activity. In addition, binding of YAP to the <i>MMP24</i> promoter was confirmed by the chromatin immunoprecipitation (ChIP) assay. These results show that ECM stiffening promotes YAP activation, thereby inducing <i>MMP24</i> expression. Based on the Human Protein Atlas database, breast cancer patients with lower <i>MMP24</i> expression exhibit the worse survival rates overall. Thus, <i>MMP24</i> may negatively regulate the aggressiveness of cancer cells under the stiff ECM environment during tumor progression.https://www.mdpi.com/2306-5354/7/1/18mmpyapecmmechanical signal transductioncancer progressionprognosis |
| spellingShingle | Wataru Sugimoto Katsuhiko Itoh Hiroaki Hirata Yoshinori Abe Takeru Torii Yasumasa Mitsui Yemima Budirahardja Nobuyuki Tanaka Keiko Kawauchi MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients Bioengineering mmp yap ecm mechanical signal transduction cancer progression prognosis |
| title | MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients |
| title_full | MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients |
| title_fullStr | MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients |
| title_full_unstemmed | MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients |
| title_short | MMP24 as a Target of YAP is a Potential Prognostic Factor in Cancer Patients |
| title_sort | mmp24 as a target of yap is a potential prognostic factor in cancer patients |
| topic | mmp yap ecm mechanical signal transduction cancer progression prognosis |
| url | https://www.mdpi.com/2306-5354/7/1/18 |
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