期刊
BRITISH JOURNAL OF CANCER
卷 114, 期 5, 页码 545-553出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2016.18
关键词
arpin; breast cancer; prognosis; Arp2/3; WAVE complex
类别
资金
- Institut National du Cancer [INCA_6521]
- Fondation ARC pour la Recherche sur le Cancer [PGA120140200831]
- Comite departemental des Hauts-de-Seine de la Ligue Nationale Contre le Cancer
- educational fellowship [SP-6587.2013.4]
- RFBR grant [14-04-91056CNRC_a]
- Canceropole Ile-de-France
- [ANR-11-BSV8-0010-02]
Background: The Arp2/3 complex is required for cell migration and invasion. The Arp2/3 complex and its activators, such as the WAVE complex, are deregulated in diverse cancers. Here we investigate the expression of Arpin, the Arp2/3 inhibitory protein that antagonises the WAVE complex. Methods: We used qRT-PCR and reverse phase protein arrays in a patient cohort with known clinical parameters and outcome, immunofluorescence in breast biopsy cryosections and breast cancer cell lines. Results: Arpin was downregulated at the mRNA and protein levels in mammary carcinoma cells. Arpin mRNA downregulation was associated with poor metastasis-free survival (MFS) on univariate analysis (P = 0.022). High expression of the NCKAP1 gene that encodes a WAVE complex subunit was also associated with poor MFS on univariate analysis (P = 0.0037) and was mutually exclusive with Arpin low. Arpin low or NCKAP1 high was an independent prognosis factor on multivariate analysis (P = 0.0012) and was strongly associated with poor MFS (P = 0.000064). Conclusions: Loss of the Arp2/3 inhibitory protein Arpin produces a similar poor outcome in breast cancer as high expression of the NCKAP1 subunit of the Arp2/3 activatory WAVE complex.
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