Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068355/ https://www.ncbi.nlm.nih.gov/pubmed/29704427 http://dx.doi.org/10.1002/1878-0261.12311 |
_version_ | 1783343251967705088 |
---|---|
author | Li, Yongfei Chu, Jiahui Li, Jun Feng, Wanting Yang, Fan Wang, Yifan Zhang, Yanhong Sun, Chunxiao Yang, Mengzhu Vasilatos, Shauna N. Huang, Yi Fu, Ziyi Yin, Yongmei |
author_facet | Li, Yongfei Chu, Jiahui Li, Jun Feng, Wanting Yang, Fan Wang, Yifan Zhang, Yanhong Sun, Chunxiao Yang, Mengzhu Vasilatos, Shauna N. Huang, Yi Fu, Ziyi Yin, Yongmei |
author_sort | Li, Yongfei |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6068355 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60683552018-08-03 Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway Li, Yongfei Chu, Jiahui Li, Jun Feng, Wanting Yang, Fan Wang, Yifan Zhang, Yanhong Sun, Chunxiao Yang, Mengzhu Vasilatos, Shauna N. Huang, Yi Fu, Ziyi Yin, Yongmei Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2018-06-14 2018-08 /pmc/articles/PMC6068355/ /pubmed/29704427 http://dx.doi.org/10.1002/1878-0261.12311 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Li, Yongfei Chu, Jiahui Li, Jun Feng, Wanting Yang, Fan Wang, Yifan Zhang, Yanhong Sun, Chunxiao Yang, Mengzhu Vasilatos, Shauna N. Huang, Yi Fu, Ziyi Yin, Yongmei Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway |
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 | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068355/ https://www.ncbi.nlm.nih.gov/pubmed/29704427 http://dx.doi.org/10.1002/1878-0261.12311 |
work_keys_str_mv | AT liyongfei cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT chujiahui cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT lijun cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT fengwanting cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT yangfan cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT wangyifan cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT zhangyanhong cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT sunchunxiao cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT yangmengzhu cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT vasilatosshaunan cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT huangyi cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT fuziyi cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway AT yinyongmei cancertestisantigenplac1promotesinvasionandmetastasisofbreastcancerthroughfurinnicdptensignalingpathway |