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XB-ART-55872
Br J Cancer January 1, 2019; 120 (9): 931-940.

ECT2 associated to PRICKLE1 are poor-prognosis markers in triple-negative breast cancer.

Daulat AM , Finetti P , Revinski D , Silveira Wagner M , Camoin L , Audebert S , Birnbaum D , Kodjabachian L , Borg JP , Bertucci F .


Abstract
BACKGROUND: Triple-negative breast cancers (TNBC) are poor-prognosis tumours candidate to chemotherapy as only systemic treatment. We previously found that PRICKLE1, a prometastatic protein involved in planar cell polarity, is upregulated in TNBC. We investigated the protein complex associated with PRICKLE1 in TNBC to identify proteins possibly involved in metastatic dissemination, which might provide new prognostic and/or therapeutic targets. METHODS: We used a proteomic approach to identify protein complexes associated with PRICKLE1. The mRNA expression levels of the corresponding genes were assessed in 8982 patients with invasive primary breast cancer. We then characterised the molecular interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. Finally, experiments in Xenopus were carried out to determine their evolutionarily conserved interaction. RESULTS: Among the PRICKLE1 proteins network, we identified several small G-protein regulators. Combined analysis of the expression of PRICKLE1 and small G-protein regulators had a strong prognostic value in TNBC. Notably, the combined expression of ECT2 and PRICKLE1 provided a worst prognosis than PRICKLE1 expression alone in TNBC. PRICKLE1 regulated ECT2 activity and this interaction was evolutionary conserved. CONCLUSIONS: This work supports the idea that an evolutionarily conserved signalling pathway required for embryogenesis and activated in cancer may represent a suitable therapeutic target.

PubMed ID: 30971775
PMC ID: PMC6734648
Article link: Br J Cancer


Species referenced: Xenopus
Genes referenced: ect2 prickle1 rac1 rho tgfb1

Disease Ontology terms: breast cancer
OMIMs: BREAST CANCER

Article Images: [+] show captions
References [+] :
Abreu-Blanco, Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair. 2014, Pubmed