The oncogenic TBC domain protein USP6/TRE17 regulates cell migration and cytokinesis



Background information

Cancer cells are characterized by their intrinsic ability to rapidly divide and migrate and to invade other tissues. How these processes are regulated at a molecular level is largely unknown.


Here, we identify the oncogenic TBC (Tre-2/Bub2/Cdc16) domain protein USP6 (also termed TRE17) as a regulator of both cell migration and division. We show that manipulating USP6 expression levels alters the ability of cells to migrate and to divide. Furthermore, we observe that cell proliferation and progression through cytokinesis depend on USP6 expression via a pathway that involves the small GTPase Arf6 and its GTPase-activating protein ACAP1.


Our data suggest a model whereby the oncogenic potential of USP6 is linked to its ability to integrate cell migration and cytokinesis by regulating Arf6/ACAP1.