PubMed:28343944 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PubMed/sourceid/28343944","sourcedb":"PubMed","sourceid":"28343944","text":"RACK1 cooperates with NRAS(Q61K) to promote melanoma in vivo.\nMelanoma 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::NRas(Q61K) 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.","tracks":[{"project":"kaiyin_test","denotations":[{"id":"T1","span":{"begin":634,"end":639},"obj":"Gene"},{"id":"T2","span":{"begin":640,"end":650},"obj":"Var"},{"id":"T3","span":{"begin":687,"end":694},"obj":"NegReg"},{"id":"T4","span":{"begin":695,"end":707},"obj":"MPA"},{"id":"T5","span":{"begin":712,"end":719},"obj":"Reg"},{"id":"T6","span":{"begin":720,"end":740},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T3"},{"id":"R4","pred":"CauseOf","subj":"T2","obj":"T5"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T5"}],"attributes":[{"subj":"T1","pred":"source","obj":"kaiyin_test"},{"subj":"T2","pred":"source","obj":"kaiyin_test"},{"subj":"T3","pred":"source","obj":"kaiyin_test"},{"subj":"T4","pred":"source","obj":"kaiyin_test"},{"subj":"T5","pred":"source","obj":"kaiyin_test"},{"subj":"T6","pred":"source","obj":"kaiyin_test"}]},{"project":"name_no","denotations":[{"id":"T1","span":{"begin":634,"end":639},"obj":"Gene"},{"id":"T2","span":{"begin":640,"end":650},"obj":"Var"},{"id":"T3","span":{"begin":687,"end":694},"obj":"NegReg"},{"id":"T4","span":{"begin":695,"end":707},"obj":"MPA"},{"id":"T5","span":{"begin":712,"end":719},"obj":"Reg"},{"id":"T6","span":{"begin":720,"end":740},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T1","obj":"T2"},{"id":"R2","pred":"CauseOf","subj":"T2","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T3"},{"id":"R4","pred":"CauseOf","subj":"T2","obj":"T5"},{"id":"R5","pred":"ThemeOf","subj":"T6","obj":"T5"}],"attributes":[{"subj":"T1","pred":"source","obj":"name_no"},{"subj":"T2","pred":"source","obj":"name_no"},{"subj":"T3","pred":"source","obj":"name_no"},{"subj":"T4","pred":"source","obj":"name_no"},{"subj":"T5","pred":"source","obj":"name_no"},{"subj":"T6","pred":"source","obj":"name_no"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"kaiyin_test","color":"#d6ec93","default":true},{"id":"name_no","color":"#e893ec"}]}]}}