Abrogation of RAB27A expression transiently affects melanoma cell proliferation

The role of the small GTPase RAB27A as an essential melanosome trafficking regulator in melanocytes is well-accepted. Based on copy number and gene expression data in early passage melanoma cell lines, RAB27A was identified as a driver gene that promotes melanoma progression. RAB27A has also been linked to another propeller of cancer progression: exosome secretion. We have recently demonstrated that RAB27A is overexpressed in a subset of melanomas. High RAB27A gene and protein expression correlates with poor prognosis in melanoma patients. Mechanistic investigations revealed that the generation of pro-invasive exosomes was RAB27A-dependent and, therefore, silencing RAB27A reduced melanoma cell invasion in vitro and in vivo. However, previous studies have implicated RAB27A to be involved in both proliferation and invasion of melanoma cells. In this study, we demonstrate that the effects of abrogating RAB27A expression on proliferation are temporary, while the effects on tumor invasion and metastasis are persistent. Herein, we dissect the short-term versus long-term effects of RAB27A knockdown on melanoma cell proliferation, invasion, and metastasis. We believe that our findings provide novel insights into the effects of RAB27A blockade.