RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation
Abstract Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti‐metastatic drugs are still limited. Here it is reported that the RNA‐binding protein RBMS1 is positively associated with increased lymph node metastasis in non‐small cell lung cancer (NSCLC). Depl...
| Principais autores: | , , , , , , , , , , , , , , , , |
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| Formato: | Artigo |
| Idioma: | English |
| Publicado em: |
Wiley
2024-04-01
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| coleção: | Advanced Science |
| Assuntos: | |
| Acesso em linha: | https://doi.org/10.1002/advs.202307122 |
| _version_ | 1827233437197533184 |
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| author | Yu Sun Dan Chen Siwen Sun Menglin Ren Liang Zhou Chaoqun Chen Jinyao Zhao Huanhuan Wei Qingzhi Zhao Yangfan Qi Jinrui Zhang Ge Zhang Han Liu Qingkai Yang Quentin Liu Yang Wang Wenjing Zhang |
| author_facet | Yu Sun Dan Chen Siwen Sun Menglin Ren Liang Zhou Chaoqun Chen Jinyao Zhao Huanhuan Wei Qingzhi Zhao Yangfan Qi Jinrui Zhang Ge Zhang Han Liu Qingkai Yang Quentin Liu Yang Wang Wenjing Zhang |
| author_sort | Yu Sun |
| collection | DOAJ |
| description | Abstract Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti‐metastatic drugs are still limited. Here it is reported that the RNA‐binding protein RBMS1 is positively associated with increased lymph node metastasis in non‐small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC. |
| first_indexed | 2024-04-24T08:03:52Z |
| format | Article |
| id | doaj.art-723fd7e34f2340828b252270dad66afd |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2025-03-21T19:33:19Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-723fd7e34f2340828b252270dad66afd2024-06-03T14:05:50ZengWileyAdvanced Science2198-38442024-04-011115n/an/a10.1002/advs.202307122RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P TranslationYu Sun0Dan Chen1Siwen Sun2Menglin Ren3Liang Zhou4Chaoqun Chen5Jinyao Zhao6Huanhuan Wei7Qingzhi Zhao8Yangfan Qi9Jinrui Zhang10Ge Zhang11Han Liu12Qingkai Yang13Quentin Liu14Yang Wang15Wenjing Zhang16Sino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaDepartment of Pathology the First Affiliated Hospital of Dalian Medical University Dalian Medical University Dalian 116011 ChinaDepartment of Oncology & Sino‐US Research Center for Cancer Translational Medicine the Second Affiliated Hospital Dalian Medical University Dalian 116023 ChinaSino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaSino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaSino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaCAS Key Laboratory of Computational Biology Bio‐Med Big Data Center Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaSino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaDepartment of Immunology College of Basic Medical Sciences Dalian Medical University Dalian 116044 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaSino‐US Research Center for Cancer Translational Medicine of the Second Affiliated Hospital of Dalian Medical University & Institute of Cancer Stem Cell Dalian Medical University Dalian 116023 ChinaInstitute of Cancer Stem Cell Dalian Medical University Dalian 116044 ChinaAbstract Metastasis is the leading cause for the high mortality of lung cancer, however, effective anti‐metastatic drugs are still limited. Here it is reported that the RNA‐binding protein RBMS1 is positively associated with increased lymph node metastasis in non‐small cell lung cancer (NSCLC). Depletion of RBMS1 suppresses cancer cell migration and invasion in vitro and inhibits cancer cell metastasis in vivo. Mechanistically, RBMS1 interacts with YTHDF1 to promote the translation of S100P, thereby accelerating NSCLC cell metastasis. The RRM2 motif of RBMS1 and the YTH domain of YTHDF1 are required for the binding of RBMS1 and YTHDF1. RBMS1 ablation inhibits the translation of S100P and suppresses tumor metastasis. Targeting RBMS1 with NTP, a small molecular chemical inhibitor of RBMS1, attenuates tumor metastasis in a mouse lung metastasis model. Correlation studies in lung cancer patients further validate the clinical relevance of the findings. Collectively, the study provides insight into the molecular mechanism by which RBMS1 promotes NSCLC metastasis and offers a therapeutic strategy for metastatic NSCLC.https://doi.org/10.1002/advs.202307122lung cancermetastasisRBMS1RNA binding protein |
| spellingShingle | Yu Sun Dan Chen Siwen Sun Menglin Ren Liang Zhou Chaoqun Chen Jinyao Zhao Huanhuan Wei Qingzhi Zhao Yangfan Qi Jinrui Zhang Ge Zhang Han Liu Qingkai Yang Quentin Liu Yang Wang Wenjing Zhang RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation Advanced Science lung cancer metastasis RBMS1 RNA binding protein |
| title | RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation |
| title_full | RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation |
| title_fullStr | RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation |
| title_full_unstemmed | RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation |
| title_short | RBMS1 Coordinates with the m6A Reader YTHDF1 to Promote NSCLC Metastasis through Stimulating S100P Translation |
| title_sort | rbms1 coordinates with the m6a reader ythdf1 to promote nsclc metastasis through stimulating s100p translation |
| topic | lung cancer metastasis RBMS1 RNA binding protein |
| url | https://doi.org/10.1002/advs.202307122 |
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