Abstract：
:Although common cancer hallmarks are well established, lineage-restricted oncogenes remain less understood. Here, we report an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF, the best-characterized melanocyte lineage-specific transcription factor. Instead, we describe the neuroectodermal master modulator SOX10 and the oncogene MYC as RAB7 regulators. These results reveal a unique wiring of the lysosomal pathway that melanomas exploit to foster tumor progression.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Alonso-Curbelo D,Riveiro-Falkenbach E,Pérez-Guijarro E,Cifdaloz M,Karras P,Osterloh L,Megías D,Cañón E,Calvo TG,Olmeda D,Gómez-López G,Graña O,Sánchez-Arévalo Lobo VJ,Pisano DG,Wang HW,Ortiz-Romero P,Tormo D,Hoek K,Rodoi
10.1016/j.ccr.2014.04.030subject
Has Abstractpub_date
2014-07-14 00:00:00pages
61-76issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(14)00218-9journal_volume
26pub_type
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