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Article Dans Une Revue Cellular Signalling Année : 2017

RACK1 cooperates with NRASQ61K to promote melanoma in vivo

Edouard Reyes-Gomez
Jacky Ezagal
  • Fonction : Auteur
  • PersonId : 1204002
P.H. Commere
Uwe Maskos

Résumé

Melanoma is the deadliest skin cancer. RACK1 (Receptor for activated protein kinase C) protein was proposed as a biological marker of melanoma in human and domestic animal species harboring spontaneous melanomas. As a scaffold protein, RACK1 is able to coordinate the interaction of key signaling molecules implicated in both physiological cellular functions and tumorigenesis. A role for RACK1 in rewiring ERK and JNK signaling pathways in melanoma cell lines had been proposed. Here, we used a genetic approach to test this hypothesis in vivo in the mouse. We show that Rack1 knock-down in the mouse melanoma cell line B16 reduces invasiveness and induces cell differentiation. We have developed the first mouse model for RACK1 gain of function, Tyr::Rack1-HA transgenic mice, targeting RACK1 to melanocytes in vivo. RACK1 overexpression was not sufficient to initiate melanomas despite activated ERK and AKT. However, in a context of melanoma predisposition, RACK1 overexpression reduced latency and increased incidence and metastatic rate. In primary melanoma cells from Tyr::Rack1-HA, Tyr::NRasQ61K mice, activated JNK (c-Jun N-terminal kinase) and activated STAT3 (signal transducer and activator of transcription 3) acted as RACK1 oncogenic partners in tumoral progression. A sequential and coordinated activation of ERK, JNK and STAT3 with RACK1 is shown to accelerate aggressive melanoma development in vivo.
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Dates et versions

hal-01529469 , version 1 (26-09-2017)

Identifiants

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Cécile Campagne, Edouard Reyes-Gomez, M.E. Picco, Sophia Loiodice, Paul Salaun, et al.. RACK1 cooperates with NRASQ61K to promote melanoma in vivo. Cellular Signalling, 2017, In Press, ⟨10.1016/j.cellsig.2017.03.015⟩. ⟨hal-01529469⟩
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