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

By Avais M. Daulat, Pascal Finetti, Diego Revinski, Mônica Silveira Wagner, Luc Camoin, Stephane Audebert, Daniel Birnbaum, Laurent Kodjabachian, Jean-Paul Borg, François Bertucci

Posted 14 Dec 2018
bioRxiv DOI: 10.1101/496026 (published DOI: 10.1038/s41416-019-0448-z)

Background: Triple-negative breast cancers are poor-prognosis tumors characterized by absence of molecular signature and are chemotherapy is still the only systemic treatment. Currently, research focus to identify biomarkers that may be usable for prognosis and/or for treatment, notably among the proteins involved in cell migration and metastatic capacity. Methods: We used proteomic approach to identify protein complexes associated to PRICKLE1 and the mRNA expression level of the corresponding genes in a retrospective series of 8,982 clinically annotated patients with invasive primary breast cancer were assessed. Then, we characterize molecularly the interaction between PRICKLE1 and the guanine nucleotide exchange factor ECT2. Finally, experiments in Xenopus have been carrying out to determine their evolutionary conserved interaction. Results: We have identified a network of proteins interacting with the prometastatic scaffold protein PRICKLE1 that includes several small G-protein regulators involved in cell migration and metastasis. Combined analysis expression of PRICKLE1 and small G-protein regulators expression has a strong prognostic value in TNBC. We show that PRICKLE1 controls the activity of ECT2 on RAC1 signaling, a pathway required for cancer cell dissemination. Conclusions: This work supports the idea that promigratory proteins, which are overexpressed in cancerous epithelium, are suitable pharmaceutical targets.

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