Yinshen Wee

Abstract The intrinsic ability of cancer cells to evade death underpins tumorigenesis, progression, metastasis, and the survival of drug-tolerant persister (DTP) cells. Herein, we discovered that the small GTPase ARF6 plays a central role in tumor survival by fortifying RAF oncoprotein levels. ARF6 activation was sufficient to increase BRAFV600E, ARAF, and CRAF proteins through a post-transcriptional mechanism, while sustained inhibition of ARF6 eventually led to decay.

Abstract Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development.

Abstract Adaptive immune resistance (AIR) is a protective process used by cancer to escape elimination by CD8+ T cells. Inhibition of immune checkpoints PD-1 and CTLA-4 specifically target Interferon-gamma (IFNγ)-driven AIR. AIR begins at the plasma membrane where tumor cell-intrinsic cytokine signaling is initiated. Thus, plasma membrane remodeling by endomembrane trafficking could regulate AIR.