MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells
Abstract Background Immunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2542 |
| _version_ | 1797264994248687616 |
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| author | Gangling Tong Boran Cheng Jingzhang Li Xuan Wu Qiaohong Nong Lirui He Xi Li Laiqing Li Shubin Wang |
| author_facet | Gangling Tong Boran Cheng Jingzhang Li Xuan Wu Qiaohong Nong Lirui He Xi Li Laiqing Li Shubin Wang |
| author_sort | Gangling Tong |
| collection | DOAJ |
| description | Abstract Background Immunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity. Methods The expression of MACC1, c‐Met, and PDL1 in human GC tissues was first assessed using quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c‐Met, and PDL1 using RT‐PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo. Results We found that expression of MACC1, c‐Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c‐Met and PDL1 expression levels, and c‐Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo. Conclusions From these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy. |
| first_indexed | 2024-04-25T00:37:44Z |
| format | Article |
| id | doaj.art-8af6ff75625b4c9a827ffd6ccfb7e46e |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-25T00:37:44Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-8af6ff75625b4c9a827ffd6ccfb7e46e2024-03-12T14:35:42ZengWileyCancer Medicine2045-76342019-11-018167044705410.1002/cam4.2542MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cellsGangling Tong0Boran Cheng1Jingzhang Li2Xuan Wu3Qiaohong Nong4Lirui He5Xi Li6Laiqing Li7Shubin Wang8Department of Oncology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Oncology Liuzhou People's Hospital Liuzhou ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaGuangzhou Youdi Bio‐technology Co., Ltd Guangzhou ChinaDepartment of Oncology Peking University Shenzhen Hospital Shenzhen ChinaAbstract Background Immunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity. Methods The expression of MACC1, c‐Met, and PDL1 in human GC tissues was first assessed using quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c‐Met, and PDL1 using RT‐PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo. Results We found that expression of MACC1, c‐Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c‐Met and PDL1 expression levels, and c‐Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo. Conclusions From these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.https://doi.org/10.1002/cam4.2542c‐Met/AKT/mTOR pathwaygastric cancerMACC1PDL1tumor immunity |
| spellingShingle | Gangling Tong Boran Cheng Jingzhang Li Xuan Wu Qiaohong Nong Lirui He Xi Li Laiqing Li Shubin Wang MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells Cancer Medicine c‐Met/AKT/mTOR pathway gastric cancer MACC1 PDL1 tumor immunity |
| title | MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells |
| title_full | MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells |
| title_fullStr | MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells |
| title_full_unstemmed | MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells |
| title_short | MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells |
| title_sort | macc1 regulates pdl1 expression and tumor immunity through the c met akt mtor pathway in gastric cancer cells |
| topic | c‐Met/AKT/mTOR pathway gastric cancer MACC1 PDL1 tumor immunity |
| url | https://doi.org/10.1002/cam4.2542 |
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