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

Authors:
Avais M Daulat
Avais M Daulat
Université Paris Descartes
France
Pascal Finetti
Pascal Finetti
Marseille Cancer Research Center (CRCM)
France
Diego Revinski
Diego Revinski
Equipe labellisée 'Cell polarity
Luc Camoin
Luc Camoin
Université Paris Descartes
France
Stephane Audebert
Stephane Audebert
Institut Hospitalier Universitaire Marseille
France
Daniel Birnbaum
Daniel Birnbaum
Aix-Marseille Université
Marseille | France
Laurent Kodjabachian
Laurent Kodjabachian
Aix-Marseille Université
France

Br J Cancer 2019 Apr 11;120(9):931-940. Epub 2019 Apr 11.

Centre de Recherche en Cancérologie de Marseille, Equipe labellisée 'Predictive oncology' Ligue 2018, Aix Marseille Université, Inserm, CNRS, Institut Paoli Calmettes, 13009, Marseille, France.

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.

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http://dx.doi.org/10.1038/s41416-019-0448-zDOI Listing
April 2019
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References

(Supplied by CrossRef)
Article in Front. Oncol.
CWS Tong et al.
Front. Oncol. 2018
Article in Dev. Cell
AM Daulat et al.
Dev. Cell 2016
Article in Nat. Rev. Mol. Cell Biol.
MT Butler et al.
Nat. Rev. Mol. Cell Biol. 2017
Article in Semin. Cell Dev. Biol.
SY Sokol et al.
Semin. Cell Dev. Biol. 2015
Article in J. Embryol. Exp. Morphol.
D Gubb et al.
J. Embryol. Exp. Morphol. 1982
Article in Curr. Biol.
MT Veeman et al.
Curr. Biol. 2003
Article in Curr. Biol.
M Takeuchi et al.
Curr. Biol. 2003
Article in EMBO J.
A Jenny et al.
EMBO J. 2003
Article in Cell
V Luga et al.
Cell 2012
Article in Nat. Commun.
L Zhang et al.
Nat. Commun. 2016
Article in J. Cell Sci.
BC Lim et al.
J. Cell Sci. 2016

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