MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination
Abstract Mitogen- and stress-activated protein kinase 1 (MSK1), a Ser/Thr kinase, phosphorylates nuclear proteins to increase their stability and DNA-binding affinity. Despite the role of MSK1 in promoting cancer progression in colorectal cancer (CRC), the precise molecular mechanisms remain uneluci...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-025-01433-0 |
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| author | Keun-Seok Hong Ki-Jun Ryu Hyemin Kim Minju Kim Seung-Ho Park Taeyoung Kim Jung Wook Yang Cheol Hwangbo Kwang Dong Kim Young-Jun Park Jiyun Yoo |
| author_facet | Keun-Seok Hong Ki-Jun Ryu Hyemin Kim Minju Kim Seung-Ho Park Taeyoung Kim Jung Wook Yang Cheol Hwangbo Kwang Dong Kim Young-Jun Park Jiyun Yoo |
| author_sort | Keun-Seok Hong |
| collection | DOAJ |
| description | Abstract Mitogen- and stress-activated protein kinase 1 (MSK1), a Ser/Thr kinase, phosphorylates nuclear proteins to increase their stability and DNA-binding affinity. Despite the role of MSK1 in promoting cancer progression in colorectal cancer (CRC), the precise molecular mechanisms remain unelucidated. Here we show that MSK1 expression induces the epithelial–mesenchymal transition (EMT) process and increases CRC cell metastasis. Furthermore, we discovered that MSK1 interacts with Snail, a key EMT regulator, and increases its stability by inhibiting ubiquitin-mediated proteasomal degradation. Importantly, MSK1 increased Snail protein stability by promoting deubiquitination rather than inhibiting its ubiquitination. Finally, we identified USP5 as an essential deubiquitinase that binds to Snail protein phosphorylated by MSK1. Based on the experimental data, in CRC, MSK1–Snail–USP5 axis can promote EMT and metastasis of CRC. Together, our findings provide potential biomarkers and novel therapeutic targets for further research in CRC. |
| format | Article |
| id | doaj-art-15130b40d99d4d15989329d75bce71ea |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-15130b40d99d4d15989329d75bce71ea2025-08-20T03:52:19ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132025-04-0157482083510.1038/s12276-025-01433-0MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitinationKeun-Seok Hong0Ki-Jun Ryu1Hyemin Kim2Minju Kim3Seung-Ho Park4Taeyoung Kim5Jung Wook Yang6Cheol Hwangbo7Kwang Dong Kim8Young-Jun Park9Jiyun Yoo10Department of Bio and Medical Bigdata (Brain Korea 21 Four), Gyeongsang National UniversityDepartment of Biochemistry and Institute of Health Sciences, Gyeongsang National University School of MedicineAnti-aging Bio Cell Factory Regional Leading Research Center, Gyeongsang National UniversityDivision of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National UniversityEnvironmental Disease Research Center, Korea Research Institute of Bioscience and BiotechnologyDivision of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National UniversityDepartment of Pathology, Gyeongsang National University Hospital, Gyeongsang National University College of MedicineDivision of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National UniversityDivision of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National UniversityEnvironmental Disease Research Center, Korea Research Institute of Bioscience and BiotechnologyDivision of Applied Life Science (Brain Korea 21 Four), Research Institute of Life Sciences, Gyeongsang National UniversityAbstract Mitogen- and stress-activated protein kinase 1 (MSK1), a Ser/Thr kinase, phosphorylates nuclear proteins to increase their stability and DNA-binding affinity. Despite the role of MSK1 in promoting cancer progression in colorectal cancer (CRC), the precise molecular mechanisms remain unelucidated. Here we show that MSK1 expression induces the epithelial–mesenchymal transition (EMT) process and increases CRC cell metastasis. Furthermore, we discovered that MSK1 interacts with Snail, a key EMT regulator, and increases its stability by inhibiting ubiquitin-mediated proteasomal degradation. Importantly, MSK1 increased Snail protein stability by promoting deubiquitination rather than inhibiting its ubiquitination. Finally, we identified USP5 as an essential deubiquitinase that binds to Snail protein phosphorylated by MSK1. Based on the experimental data, in CRC, MSK1–Snail–USP5 axis can promote EMT and metastasis of CRC. Together, our findings provide potential biomarkers and novel therapeutic targets for further research in CRC.https://doi.org/10.1038/s12276-025-01433-0 |
| spellingShingle | Keun-Seok Hong Ki-Jun Ryu Hyemin Kim Minju Kim Seung-Ho Park Taeyoung Kim Jung Wook Yang Cheol Hwangbo Kwang Dong Kim Young-Jun Park Jiyun Yoo MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination Experimental and Molecular Medicine |
| title | MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination |
| title_full | MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination |
| title_fullStr | MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination |
| title_full_unstemmed | MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination |
| title_short | MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination |
| title_sort | msk1 promotes colorectal cancer metastasis by increasing snail protein stability through usp5 mediated snail deubiquitination |
| url | https://doi.org/10.1038/s12276-025-01433-0 |
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