Abrogation of RAB27A expression transiently affects melanoma cell proliferation

Abstract

The role of the small GTPase RAB27A as an essential melanosome trafficking regulator in melanocytes is well-accepted. A decade ago, RAB27A was identified as a tumor dependency gene that promotes melanoma cell proliferation. RAB27A has since 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, in contrast to the previously reported persistent effects on tumor invasion and metastasis. Therefore, we assist in the dissection of 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. SignificanceRAB27A is known to serve as an essential regulator for melanosome trafficking. However, to date its role in melanoma biology has not been completely deciphered. While there are consistent independent reports on the pro-invasive effects of RAB27A, there are conflicting data on its impact on cell proliferation. Here we show that indeed abrogation of RAB27A does reduce cellular proliferation; however, this effect is only transient, while the impact on invasion as reported previously is persistent. This finding offers an explanation for the apparent contradiction in the literature and provides a deeper understanding of RAB27A function in melanoma cell biology.