Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway
Placenta‐specific protein 1 (Plac1) is a cancer/testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remain elusive. Here, we report that Plac1 is an important oncogenic and prognosti...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-08-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.12311 |
| _version_ | 1819207091615694848 |
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| author | Yongfei Li Jiahui Chu Jun Li Wanting Feng Fan Yang Yifan Wang Yanhong Zhang Chunxiao Sun Mengzhu Yang Shauna N. Vasilatos Yi Huang Ziyi Fu Yongmei Yin |
| author_facet | Yongfei Li Jiahui Chu Jun Li Wanting Feng Fan Yang Yifan Wang Yanhong Zhang Chunxiao Sun Mengzhu Yang Shauna N. Vasilatos Yi Huang Ziyi Fu Yongmei Yin |
| author_sort | Yongfei Li |
| collection | DOAJ |
| description | Placenta‐specific protein 1 (Plac1) is a cancer/testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remain elusive. Here, we report that Plac1 is an important oncogenic and prognostic factor, which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, hormone receptor status, and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co‐immunoprecipitation and immunofluorescence cell staining assays revealed that interaction of Plac1 and Furin degraded Notch1 and generated Notch1 intracellular domain (NICD) that could inhibit PTEN activity. These findings are consistent with the results of microarray study in MDA‐MB‐231 cells overexpressing Plac1. A rescue study showed that inhibition of Furin and overexpression of PTEN in Plac1 overexpression cells blocked Plac1‐induced tumor cell progression. Taken together, our findings suggest that functional interaction between Plac1 and Furin enhances breast cancer invasion and metastasis and the Furin/NICD/PTEN axis may act as an important therapeutic target for breast cancer treatment. |
| first_indexed | 2024-12-23T05:17:59Z |
| format | Article |
| id | doaj.art-d17895e6b1d64192b6e73a428ab87d81 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-12-23T05:17:59Z |
| publishDate | 2018-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-d17895e6b1d64192b6e73a428ab87d812022-12-21T17:58:46ZengWileyMolecular Oncology1574-78911878-02612018-08-011281233124810.1002/1878-0261.12311Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathwayYongfei Li0Jiahui Chu1Jun Li2Wanting Feng3Fan Yang4Yifan Wang5Yanhong Zhang6Chunxiao Sun7Mengzhu Yang8Shauna N. Vasilatos9Yi Huang10Ziyi Fu11Yongmei Yin12Department of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Pharmacology and Chemical Biology UPMC Hillman Cancer Center University of Pittsburgh PA USADepartment of Pharmacology and Chemical Biology UPMC Hillman Cancer Center University of Pittsburgh PA USADepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaDepartment of Oncology The First Affiliated Hospital of Nanjing Medical University ChinaPlacenta‐specific protein 1 (Plac1) is a cancer/testis antigen that plays a critical role in promoting cancer initiation and progression. However, the clinical significance and mechanism of Plac1 in cancer progression remain elusive. Here, we report that Plac1 is an important oncogenic and prognostic factor, which physically interacts with Furin to drive breast cancer invasion and metastasis. We have shown that Plac1 expression positively correlates with clinical stage, lymph node metastasis, hormone receptor status, and overall patient survival. Overexpression of Plac1 promoted invasion and metastasis of breast cancer cells in vitro and in vivo. Co‐immunoprecipitation and immunofluorescence cell staining assays revealed that interaction of Plac1 and Furin degraded Notch1 and generated Notch1 intracellular domain (NICD) that could inhibit PTEN activity. These findings are consistent with the results of microarray study in MDA‐MB‐231 cells overexpressing Plac1. A rescue study showed that inhibition of Furin and overexpression of PTEN in Plac1 overexpression cells blocked Plac1‐induced tumor cell progression. Taken together, our findings suggest that functional interaction between Plac1 and Furin enhances breast cancer invasion and metastasis and the Furin/NICD/PTEN axis may act as an important therapeutic target for breast cancer treatment.https://doi.org/10.1002/1878-0261.12311breast cancercancer metastasiscancer/testis geneimmunotherapy targetsprognostic factor |
| spellingShingle | Yongfei Li Jiahui Chu Jun Li Wanting Feng Fan Yang Yifan Wang Yanhong Zhang Chunxiao Sun Mengzhu Yang Shauna N. Vasilatos Yi Huang Ziyi Fu Yongmei Yin Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway Molecular Oncology breast cancer cancer metastasis cancer/testis gene immunotherapy targets prognostic factor |
| title | Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
| title_full | Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
| title_fullStr | Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
| title_full_unstemmed | Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
| title_short | Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
| title_sort | cancer testis antigen plac1 promotes invasion and metastasis of breast cancer through furin nicd pten signaling pathway |
| topic | breast cancer cancer metastasis cancer/testis gene immunotherapy targets prognostic factor |
| url | https://doi.org/10.1002/1878-0261.12311 |
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