Arpin downregulation in breast cancer is associated with poor prognosis

作者：Lomakina Maria E; Lallemand Francois; Vacher Sophie; Molinie Nicolas; Dang Irene; Cacheux Wulfran; Chipysheva Tamara A; Ermilova Valeria D; de Koning Leanne; Dubois Thierry; Bieche Ivan; Alexandrova Antonina Y; Gautreau Alexis^*

来源：British Journal of Cancer, 2016, 114(5): 545-553.

DOI：10.1038/bjc.2016.18

• arpin
• breast cancer
• prognosis
• Arp2/3
• WAVE complex

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.

• 出版日期2016-3-1