RACK1 promotes proliferation and motility of melanoma cell lines.

VILLANUEVA MB; PICCO ME; MUÑOZ CONTRERAS I; BARBERO G; CASTRO MV; LOPEZ BERGAMI P.

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de BioCiencias; 2017

Sociedades de BioCiencias

RACK1 (Receptor for Activated C kinase 1) is a scaffold proteinthat coordinates the interaction of key signaling molecules implicatedin both physiological cellular functions and tumorigenesis.RACK1 has been shown to be aberrantly expressed in cancer whereit has either pro- or anti-oncogenic effects.Melanoma is the deadliest skin cancer and its incidence has increasedover the past three decades. The role of RACK1 in melanomahas been poorly studied. Recently, it was shown that RACK1cooperates with NRASQ61K to promote melanoma in vivo. The aimof this study is to investigate the effect of RACK1 overexpressionin melanoma. To this end we stably transfected RACK1-HA intothe melanoma cell lines SK-Mel28 and A375. To determinate theeffect of RACK1 in cell proliferation we performed Crystal Violet assays.We found that RACK1 overexpression significantly increasedthe proliferation of SK-Mel28-RACK1 and A375-RACK1 cell lines(p<0.05). To identify possible underlying mechanisms we performedWestern blots. We found that RACK1 overexpression significantlyincreased Akt phosphorylation (T308 and S473) and CyclinD1 levels (p<0.05).To study the effect of RACK1 in cell motility weperformed Wound Healing assays. These experiments showedan increase in cell motility in SK-Mel28-RACK1 and A375-RACK1(p<0.05). The increase in cell motility was in agreement with theelevated expression of the mesenchymal markers, N-cadherin andVimentin. These results suggest that RACK1 promotes proliferationand migration in melanoma and could play an important role in thetumorigenesis and aggressiveness of this disease.