Cancer/testis antigen‐Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway. Issue 8 (14th June 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Molecular oncology. Volume 12:Issue 8(2018)
• Page Start: 1233
• Page End: 1248
• Publication Date: 2018-06-14
• Subjects: breast cancer -- cancer metastasis -- cancer/testis gene -- immunotherapy targets -- prognostic factor; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12311
• Languages: English
• ISSNs: 1574-7891

Abstract

Abstract : 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. Abstract : A mechanism model for placenta‐specific protein 1 (PLAC1) promotes invasion and metastasis of breast cancer. Plac1 physically interacts with Furin, which activates Notch1 intracellular domain/Hes1/PTEN/AKT signaling pathway to promote tumor progression in human breast cancer.