Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy (Review)

Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer

“…Knockdown of Fer in addition to PLD1/PLD2 did not result in further reduction of migration, suggesting that PLD is a critical upstream regulator of Fer and cortactin phosphorylation (Itoh et al, 2009). Fes is an NRTK that shares structural similarity to Fer and is also implicated in cell migration (Kanda et al, 2007). PLD2 interacts with Fes and overexpression of PLD2 increases Fes activity (Di Fulvio et al, 2012).…”

“…PLD activity is required for leading edge formation (Santy and Casanova, 2001) and overexpression of PLD promotes leading edge characteristics (Shen et al, 2002). Actin-rich leading edge formation requires a series of cytoskeletal rearrangements coordinated by members of the Rho family such as RhoA, Cdc42, and Rac (Ridley et al, 2003) along with other proteins, such as nonreceptor tyrosine kinases (NRTKs) of the Src family (Kanda et al, 2007). Rac proteins appear to control lamellipodia formation, whereas Cdc42 controls filopodia formation (Etienne-Manneville, 2004).…”

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

“…The Src protein family is important largely in growth factor signaling (Abram and Courtneidge, 2000), but selected members are also known to regulate other aspects of cell function such as anchoring junction dynamics during spermatogenesis (Bjorge et al, 2000;Courtneidge, 2002;Abram and Lowell, 2007;Kanda et al, 2007;Rivera and Olivera, 2007;Schenone et al, 2007). Studies have shown that c-Src is expressed by both Sertoli and germ cells and that it associates with the apical ectoplasmic specialization via 1) the integrin multiprotein complex (Siu et al, 2005;, 2) myotubularin-related protein 2 (Zhang et al, 2005), and 3) laminin-333 (Fig.…”

A randomized phase II study of cediranib alone versus cediranib in combination with dasatinib in docetaxel resistant, castration resistant prostate cancer patients

“…Angiogenesis is often dysregulated in cancer and antiangiogenic molecules are now standard of treatment for several types of malignancies [79]. Activation of Src has been associated with both positive and negative regulation of VEGFR expression, with secondary inhibitory effects on permeability, endothelial cell differentiation and migration [80–84]. This activity may result in an overlapping antiangiogenic effect that can potentially explain the increased toxicity observed in our study, suggesting the need for a vigilant and prudent strategy for further combination treatment.…”