Girding for migratory cues: roles of the Akt substrate Girdin in cancer progression and angiogenesis

Abstract

Cell migration is a fundamental aspect of a multitude of physiological and pathological processes, including embryonic development, inflammation, angiogenesis, and cancer progression. A variety of proteins are essential for cell migration, but context‐specific signaling pathways and promigratory proteins must now be identified for our understanding of cancer biology to continue to advance. In this review, we focus on the emerging roles of Girdin (also designated KIAA1212, APE, GIV, and HkRP1), a novel component of the phosphatidylinositol 3‐kinase (PI3‐K)/Akt signaling pathway that is a core‐signaling transduction pathway in cancer progression. Girdin is expressed in some types of cancer cells and immature endothelial cells, and is therefore at the crossroads of multiple intracellular processes, including reorganization of the actin cytoskeleton, endocytosis, and modulation of Akt activity, which ultimately lead to cancer invasion and angiogenesis. It also acts as a nonreceptor guanine nucleotide exchange factor (GEF) for Gαi proteins. A significant observation is that Girdin, although vital for cancer progression and postnatal vascular remodelling, is dispensable for cell migratory events during embryonic development. These findings suggest that Girdin and its interacting proteins are potential pharmaceutical targets for cancer therapies and pathological anigiogenesis, including tumor angiogenesis. (Cancer Sci 2010; 101: 836–842)

Microparticles mediated cross-talk between tumoral and endothelial cells promote the constitution of a pro-metastatic vascular niche through Arf6 up regulation

“…Akt phosphorylation is known to be involved in EC proliferation, migration and tube formation [36]. Our findings and a recent study by Kawamoto et al propose that M-MPs could activate Akt phosphorylation in HUVECs [16].…”

Inhibitors of enhancer of zeste homolog 2 (EZH2) activate tumor-suppressor microRNAs in human cancer cells

“…Girdin is a component of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway, which is a pivotal signaling pathway for cancer progression and has an important role in cancer cell migration by controlling actin organization. 19 As shown in Figure 3c, expression of Girdin protein was reduced after DZNep treatment in both AGS and HepG2 cells, and this was accompanied by upregulation of miR-4448 expression.…”

A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis

“…grdn-1 encodes the C. elegans ortholog of mammalian Girdin, a signaling and scaffolding protein implicated in the regulation of diverse cellular processes including cell migration, cell division, autophagy, neurogenesis, and cancer cell metastasis (Enomoto et al, 2006; Garcia-Marcos et al, 2015; Weng et al, 2010). Recently, Girdin has also been implicated in dendritic morphogenesis in Drosophila sensory neurons (Ha et al, 2015).…”