Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma
Abstract Background FAM92A1–289(abbreviated FAM289) is recognized as one of the newly-discovered putative oncogenes. However, its role and molecular mechanisms in promoting cancer progression has not yet been elucidated. This study was performed to reveal its oncogenic functions and molecular mechan...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1393-7 |
| _version_ | 1811337725809262592 |
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| author | Xing Rong Guo Mu Yu Wu Long Jun Dai Yu Huang Meng Ye Shan Shi Nan Ma Jue Wang Hao Peng Yan Ding Qiu Fang Zhang Jun Ming Tang Xu Zhi Ruan Dong Sheng Li |
| author_facet | Xing Rong Guo Mu Yu Wu Long Jun Dai Yu Huang Meng Ye Shan Shi Nan Ma Jue Wang Hao Peng Yan Ding Qiu Fang Zhang Jun Ming Tang Xu Zhi Ruan Dong Sheng Li |
| author_sort | Xing Rong Guo |
| collection | DOAJ |
| description | Abstract Background FAM92A1–289(abbreviated FAM289) is recognized as one of the newly-discovered putative oncogenes. However, its role and molecular mechanisms in promoting cancer progression has not yet been elucidated. This study was performed to reveal its oncogenic functions and molecular mechanisms in human glioblastoma multiforme (GBM) cell models with knockdown or overexpression of FAM289 in vitro and in vivo. Methods To elucidate the molecular mechanisms underlying FAM289-mediated tumor progression, the protein-protein interaction between FAM289 and Galectin-1 was verified by co-immunoprecipitation, followed by an analysis of the expression and activity of Galectin-1-associated signaling molecules. Knockdown and overexpression of FAM289 in glioma cells were applied for investigating the effects of FAM289 on cell growth, migration and invasion. The determination of FAM289 expression was performed in specimens from various stages of human gliomas. Results FAM289-galectin-1 interaction and concomitant activation of the extracellular signal-regulated kinase (ERK) pathway participated in FAM289-mediated tumor-promoting function. Since the expression of DNA methyl transferase 1 (DNMT1) and DNA methyl transferase 3B (DNMT3B) was regulated by FAM289 in U251 and U87-MG glioma cells, Galectin-1 interaction with FAM289 may promote FAM289 protein into the cell nucleus and activate the ERK pathway, thereby upregulating DNMTs expression. Drug resistance tests indicated that FAM289-mediated TMZ resistance was through stem-like property acquisition by activating the ERK pathway. The correlation between FAM289, Galectin-1 expression and the clinical stage of gliomas was also verified in tissue samples from glioblastoma patients. Conclusions Our results suggest that high expression of FAM289 in GBM tissues correlated with poor prognosis. FAM289 contributes to tumor progression in malignant glioma by interacting with Galectin-1 thereby promoting FAM289 protein translocation into the cell nucleus. FAM289 in the nucleus activated the ERK pathway, up regulated DNMTs expression and induced stem-like property gene expression which affects drug resistance of glioma cells to TMZ. This study provided functional evidence for FAM289 to be developed as a therapeutic target for cancer treatment. |
| first_indexed | 2024-04-13T18:00:13Z |
| format | Article |
| id | doaj.art-bf1143413aae45eba81c20f64fa3be32 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T18:00:13Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-bf1143413aae45eba81c20f64fa3be322022-12-22T02:36:18ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-09-0138111910.1186/s13046-019-1393-7Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant gliomaXing Rong Guo0Mu Yu Wu1Long Jun Dai2Yu Huang3Meng Ye Shan4Shi Nan Ma5Jue Wang6Hao Peng7Yan Ding8Qiu Fang Zhang9Jun Ming Tang10Xu Zhi Ruan11Dong Sheng Li12Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineCollege of Basic Medicine, Hubei University of MedicineDepartment of Neurosurgery, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineCollege of Basic Medicine, Hubei University of MedicineCollege of Basic Medicine, Hubei University of MedicineHubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of MedicineAbstract Background FAM92A1–289(abbreviated FAM289) is recognized as one of the newly-discovered putative oncogenes. However, its role and molecular mechanisms in promoting cancer progression has not yet been elucidated. This study was performed to reveal its oncogenic functions and molecular mechanisms in human glioblastoma multiforme (GBM) cell models with knockdown or overexpression of FAM289 in vitro and in vivo. Methods To elucidate the molecular mechanisms underlying FAM289-mediated tumor progression, the protein-protein interaction between FAM289 and Galectin-1 was verified by co-immunoprecipitation, followed by an analysis of the expression and activity of Galectin-1-associated signaling molecules. Knockdown and overexpression of FAM289 in glioma cells were applied for investigating the effects of FAM289 on cell growth, migration and invasion. The determination of FAM289 expression was performed in specimens from various stages of human gliomas. Results FAM289-galectin-1 interaction and concomitant activation of the extracellular signal-regulated kinase (ERK) pathway participated in FAM289-mediated tumor-promoting function. Since the expression of DNA methyl transferase 1 (DNMT1) and DNA methyl transferase 3B (DNMT3B) was regulated by FAM289 in U251 and U87-MG glioma cells, Galectin-1 interaction with FAM289 may promote FAM289 protein into the cell nucleus and activate the ERK pathway, thereby upregulating DNMTs expression. Drug resistance tests indicated that FAM289-mediated TMZ resistance was through stem-like property acquisition by activating the ERK pathway. The correlation between FAM289, Galectin-1 expression and the clinical stage of gliomas was also verified in tissue samples from glioblastoma patients. Conclusions Our results suggest that high expression of FAM289 in GBM tissues correlated with poor prognosis. FAM289 contributes to tumor progression in malignant glioma by interacting with Galectin-1 thereby promoting FAM289 protein translocation into the cell nucleus. FAM289 in the nucleus activated the ERK pathway, up regulated DNMTs expression and induced stem-like property gene expression which affects drug resistance of glioma cells to TMZ. This study provided functional evidence for FAM289 to be developed as a therapeutic target for cancer treatment.http://link.springer.com/article/10.1186/s13046-019-1393-7Glioblastoma multiforme cellFAM289ERK pathwayDNMTs |
| spellingShingle | Xing Rong Guo Mu Yu Wu Long Jun Dai Yu Huang Meng Ye Shan Shi Nan Ma Jue Wang Hao Peng Yan Ding Qiu Fang Zhang Jun Ming Tang Xu Zhi Ruan Dong Sheng Li Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma Journal of Experimental & Clinical Cancer Research Glioblastoma multiforme cell FAM289 ERK pathway DNMTs |
| title | Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma |
| title_full | Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma |
| title_fullStr | Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma |
| title_full_unstemmed | Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma |
| title_short | Nuclear FAM289-Galectin-1 interaction controls FAM289-mediated tumor promotion in malignant glioma |
| title_sort | nuclear fam289 galectin 1 interaction controls fam289 mediated tumor promotion in malignant glioma |
| topic | Glioblastoma multiforme cell FAM289 ERK pathway DNMTs |
| url | http://link.springer.com/article/10.1186/s13046-019-1393-7 |
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