Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis
Abstract Purpose Myelin and lymphocyte protein 2 (MAL2) is mainly involved in endocytosis under physiological conditions and mediates the transport of materials across the membranes of cell and organelle. It has been reported that MAL2 is significantly upregulated in diverse cancers. This study aime...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-02993-9 |
| _version_ | 1797773963455102976 |
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| author | Lijun An Huiyuan Gong Xiaojing Yu Wangming Zhang Xiaohua Liu Xiaomin Yang Liping Shu Jielin Liu Liuqi Yang |
| author_facet | Lijun An Huiyuan Gong Xiaojing Yu Wangming Zhang Xiaohua Liu Xiaomin Yang Liping Shu Jielin Liu Liuqi Yang |
| author_sort | Lijun An |
| collection | DOAJ |
| description | Abstract Purpose Myelin and lymphocyte protein 2 (MAL2) is mainly involved in endocytosis under physiological conditions and mediates the transport of materials across the membranes of cell and organelle. It has been reported that MAL2 is significantly upregulated in diverse cancers. This study aimed to investigate the role of MAL2 in breast cancer (BC). Methods Bioinformatics analysis and Immunohistochemical assay were applied to detect the correlation between MAL2 expression in breast cancer tissues and the prognosis of breast cancer patients. Functional experiments were carried out to investigate the role of MAL2 in vitro and in vivo. The molecular mechanisms involved in MAL2-induced β-catenin and c-Myc expression and β-catenin/c-Myc-mediated enhancement of BC progression were confirmed by western blot, β-catenin inhibitor and agonist, Co-IP and immunofluorescence colocalization assays. Results Results from the cancer genome atlas (TCGA) and clinical samples confirmed a significant upregulation of MAL2 in BC tissues than in adjacent non-tumor tissues. High expression of MAL2 was associated with worse prognosis. Functional experiments demonstrated that MAL2 knockdown reduced the migration and invasion associating with EMT, increased the apoptosis of BC cells in vitro and reduced the metastatic capacity in vivo. Mechanistically, MAL2 interacts with β-catenin in BC cells. MAL2 silencing reduced the expression of β-catenin and c-Myc, while the β-catenin agonist SKL2001 partially rescued the downregulation of c-Myc and inhibition of migration and invasion caused by MAL2 knockdown in BC cells. Conclusion These observations provided evidence that MAL2 acted as a potential tumor promoter by regulating EMT and β-catenin/c-Myc axis, suggesting potential implications for anti-metastatic therapy for BC. |
| first_indexed | 2024-03-12T22:13:05Z |
| format | Article |
| id | doaj.art-8c968f4d93ce423094d2e2709b042ef6 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-12T22:13:05Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-8c968f4d93ce423094d2e2709b042ef62023-07-23T11:27:05ZengBMCCancer Cell International1475-28672023-07-0123111010.1186/s12935-023-02993-9Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axisLijun An0Huiyuan Gong1Xiaojing Yu2Wangming Zhang3Xiaohua Liu4Xiaomin Yang5Liping Shu6Jielin Liu7Liuqi Yang8Department of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityDepartment of Immunology, Basic Medical College, Guizhou Medical UniversityAbstract Purpose Myelin and lymphocyte protein 2 (MAL2) is mainly involved in endocytosis under physiological conditions and mediates the transport of materials across the membranes of cell and organelle. It has been reported that MAL2 is significantly upregulated in diverse cancers. This study aimed to investigate the role of MAL2 in breast cancer (BC). Methods Bioinformatics analysis and Immunohistochemical assay were applied to detect the correlation between MAL2 expression in breast cancer tissues and the prognosis of breast cancer patients. Functional experiments were carried out to investigate the role of MAL2 in vitro and in vivo. The molecular mechanisms involved in MAL2-induced β-catenin and c-Myc expression and β-catenin/c-Myc-mediated enhancement of BC progression were confirmed by western blot, β-catenin inhibitor and agonist, Co-IP and immunofluorescence colocalization assays. Results Results from the cancer genome atlas (TCGA) and clinical samples confirmed a significant upregulation of MAL2 in BC tissues than in adjacent non-tumor tissues. High expression of MAL2 was associated with worse prognosis. Functional experiments demonstrated that MAL2 knockdown reduced the migration and invasion associating with EMT, increased the apoptosis of BC cells in vitro and reduced the metastatic capacity in vivo. Mechanistically, MAL2 interacts with β-catenin in BC cells. MAL2 silencing reduced the expression of β-catenin and c-Myc, while the β-catenin agonist SKL2001 partially rescued the downregulation of c-Myc and inhibition of migration and invasion caused by MAL2 knockdown in BC cells. Conclusion These observations provided evidence that MAL2 acted as a potential tumor promoter by regulating EMT and β-catenin/c-Myc axis, suggesting potential implications for anti-metastatic therapy for BC.https://doi.org/10.1186/s12935-023-02993-9MAL2Breast cancerMetastasisApoptosisβ-catenin/c-Myc axis |
| spellingShingle | Lijun An Huiyuan Gong Xiaojing Yu Wangming Zhang Xiaohua Liu Xiaomin Yang Liping Shu Jielin Liu Liuqi Yang Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis Cancer Cell International MAL2 Breast cancer Metastasis Apoptosis β-catenin/c-Myc axis |
| title | Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis |
| title_full | Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis |
| title_fullStr | Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis |
| title_full_unstemmed | Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis |
| title_short | Downregulation of MAL2 inhibits breast cancer progression through regulating β-catenin/c-Myc axis |
| title_sort | downregulation of mal2 inhibits breast cancer progression through regulating β catenin c myc axis |
| topic | MAL2 Breast cancer Metastasis Apoptosis β-catenin/c-Myc axis |
| url | https://doi.org/10.1186/s12935-023-02993-9 |
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