Arpin downregulation in breast cancer is associated with poor prognosis

Maria E Lomakina; François Lallemand; Sophie Vacher; Nicolas Molinie; Irene Dang; Wulfran Cacheux; Tamara A Chipysheva; Valeria D Ermilova; Leanne de Koning; Thierry Dubois; Ivan Bièche; Antonina Y Alexandrova; Alexis Gautreau

doi:10.1038/bjc.2016.18

Arpin downregulation in breast cancer is associated with poor prognosis

Br J Cancer. 2016 Mar 1;114(5):545-53. doi: 10.1038/bjc.2016.18. Epub 2016 Feb 11.

Affiliations

¹ Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation.
² Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
³ Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France.
⁴ Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
⁵ Department of Pathology, N.N. Blokhin Cancer Research Center, Moscow 115478, Russia.
⁶ Department of Translational Research, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005 Paris, France.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Adenocarcinoma / genetics
Adenocarcinoma / metabolism
Adenoma / genetics
Adenoma / metabolism
Blotting, Western
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Carcinoma / genetics*
Carcinoma / metabolism
Carcinoma / pathology
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Line, Tumor
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Disease-Free Survival
Down-Regulation*
Estrogen Receptor alpha / metabolism
Female
Fluorescent Antibody Technique
Humans
Middle Aged
Neoplasm Metastasis
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Prognosis
Protein Array Analysis
RNA, Messenger / metabolism*
Receptor, ErbB-2 / metabolism
Receptors, Progesterone / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tumor Burden

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
ESR1 protein, human
Estrogen Receptor alpha
NCKAP1 protein, human
Nuclear Proteins
PICk1 protein, human
RNA, Messenger
Receptors, Progesterone
arpin protein, human
ERBB2 protein, human
Receptor, ErbB-2