Resumen
Transforming growth factor ß (TGFß) promotes pancreatic ductal adenocarcinoma (PDAC) primarily through its non-canonical (non-Smad) signaling arms, including signaling by the small GTPase RAC1. The human RAC1 gene also encodes for another protein, designated RAC1B, but whether this isoform also interacts with TGFß signaling has remained unknown. In a series of studies in PDAC-derived cells, we found that RAC1B also cross-talks with TGFß signaling, but unlike RAC1 antagonizes TGFß-induced responses, i.e., epithelial?mesenchymal transition, through multiple mechanisms. However, rather than being uniformly inhibitory, RAC1B selectively blocks tumor-promoting pathways, while concomitantly allowing tumor-suppressive pathways to proceed. In this review article, we discuss the specific interactions between RAC1B and TGFß signaling, which occur at multiple levels and include various components of both the canonical Smad and non-Smad pathways. In addition to emerging as a novel tumor suppressor in PDAC, RAC1B turned out to be a useful tool to dissect TGFß signaling.