Abstract
Cancers represent complex autonomous robust systems, displaying interconnectivity with feedback control. Autonomy is fueled by a cancer cell's ability to ‘secrete-and-sense’: a poorly understood phenomenon.Using an integrated systems and experimental approach, here we dissect the impact of a feedback-coupled GTPase circuit within the secretory pathway that imparts secrete-and-sense autonomy. The circuit is assembled when the Ras-superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαβγ and their corresponding GAPs and GEFs are coupled by the scaffold protein GIV/Girdin, a bona fide metastasis-related protein across a variety of solid tumors.
Published Version
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