Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance
Abstract Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting to methyl donor for the methylation of DNA, RNA and protein. However, it remains unclear whether methionine affects drug resistance by...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55769-8 |
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| author | Xia-Lu Hong Chen-Kai Huang Hui Qian Chen-Hong Ding Fang Liu Huan-Yu Hong Shu-Qing Liu Si-Han Wu Xin Zhang Wei-Fen Xie |
| author_facet | Xia-Lu Hong Chen-Kai Huang Hui Qian Chen-Hong Ding Fang Liu Huan-Yu Hong Shu-Qing Liu Si-Han Wu Xin Zhang Wei-Fen Xie |
| author_sort | Xia-Lu Hong |
| collection | DOAJ |
| description | Abstract Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting to methyl donor for the methylation of DNA, RNA and protein. However, it remains unclear whether methionine affects drug resistance by influencing YAP activity. In this study, we report that methionine deprivation remarkably suppresses the transcriptional activity of YAP–TEAD in cancer cells. Methionine promotes PRMT1-catalyzed asymmetric dimethylation at R124 of YAP (YAP R124me2a). Mimicking of YAP methylation abolishes the reduction effect of methionine-restricted diet on YAP-induced drug resistance. YAP activates the transcription of SLC43A2, the methionine transporter, to increase methionine uptake in cancer cells. Knockdown of SLC43A2 decreases the level of YAP R124me2a. BCH, the inhibitor of SLC43A2, sensitizes tumors to anticancer drugs. Thus, our results unravel the positive feedback between YAP R124 methylation and SLC43A2 that contributes to anticancer drug resistance. Disrupting this positive feedback could be a potential strategy for cancer therapy. |
| format | Article |
| id | doaj-art-da0e8ebf4b9d4ae7afbc1f4467b5e692 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-da0e8ebf4b9d4ae7afbc1f4467b5e6922025-01-05T12:38:07ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-024-55769-8Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistanceXia-Lu Hong0Chen-Kai Huang1Hui Qian2Chen-Hong Ding3Fang Liu4Huan-Yu Hong5Shu-Qing Liu6Si-Han Wu7Xin Zhang8Wei-Fen Xie9Department of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityDepartment of Gastroenterology, Changzheng Hospital, Naval Medical UniversityAbstract Yes-associated protein (YAP) activation confers resistance to chemotherapy and targeted therapy. Methionine participates in cellular processes by converting to methyl donor for the methylation of DNA, RNA and protein. However, it remains unclear whether methionine affects drug resistance by influencing YAP activity. In this study, we report that methionine deprivation remarkably suppresses the transcriptional activity of YAP–TEAD in cancer cells. Methionine promotes PRMT1-catalyzed asymmetric dimethylation at R124 of YAP (YAP R124me2a). Mimicking of YAP methylation abolishes the reduction effect of methionine-restricted diet on YAP-induced drug resistance. YAP activates the transcription of SLC43A2, the methionine transporter, to increase methionine uptake in cancer cells. Knockdown of SLC43A2 decreases the level of YAP R124me2a. BCH, the inhibitor of SLC43A2, sensitizes tumors to anticancer drugs. Thus, our results unravel the positive feedback between YAP R124 methylation and SLC43A2 that contributes to anticancer drug resistance. Disrupting this positive feedback could be a potential strategy for cancer therapy.https://doi.org/10.1038/s41467-024-55769-8 |
| spellingShingle | Xia-Lu Hong Chen-Kai Huang Hui Qian Chen-Hong Ding Fang Liu Huan-Yu Hong Shu-Qing Liu Si-Han Wu Xin Zhang Wei-Fen Xie Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance Nature Communications |
| title | Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance |
| title_full | Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance |
| title_fullStr | Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance |
| title_full_unstemmed | Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance |
| title_short | Positive feedback between arginine methylation of YAP and methionine transporter SLC43A2 drives anticancer drug resistance |
| title_sort | positive feedback between arginine methylation of yap and methionine transporter slc43a2 drives anticancer drug resistance |
| url | https://doi.org/10.1038/s41467-024-55769-8 |
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