Journal article
Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway
Molecular oncology, Vol.12(8), pp.1233-1248
08/2018
DOI: 10.1002/1878-0261.12311
PMCID: PMC6068355
PMID: 29704427
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.
Details
- Title: Subtitle
- Cancer/testis antigen-Plac1 promotes invasion and metastasis of breast cancer through Furin/NICD/PTEN signaling pathway
- Creators
- Yongfei Li - Nanjing Medical UniversityJiahui Chu - Nanjing Medical UniversityJun Li - Nanjing Medical UniversityWanting Feng - Nanjing Medical UniversityFan Yang - Nanjing Medical UniversityYifan Wang - Nanjing Medical UniversityYanhong Zhang - Nanjing Medical UniversityChunxiao Sun - Nanjing Medical UniversityMengzhu Yang - Nanjing Medical UniversityShauna N Vasilatos - UPMC Hillman Cancer CenterYi Huang - UPMC Hillman Cancer CenterZiyi Fu - Nanjing Maternity and Child Health Care HospitalYongmei Yin - Nanjing Medical University
- Resource Type
- Journal article
- Publication Details
- Molecular oncology, Vol.12(8), pp.1233-1248
- DOI
- 10.1002/1878-0261.12311
- PMID
- 29704427
- PMCID
- PMC6068355
- NLM abbreviation
- Mol Oncol
- ISSN
- 1574-7891
- eISSN
- 1878-0261
- Grant note
- DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 81172503, 81302304, 81402139, 81570804, 81572603; DOI: 10.13039/501100002949, name: Government of Jiangsu Province, award: BRA2017534; DOI: 10.13039/100007452, name: Wu Jieping Medical Foundation, award: 320.6750.17006
- Language
- English
- Date published
- 08/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383886602771
Metrics
24 Record Views