oa Editorial [Hot topic: Focal Adhesion Kinase Signaling in Cancer- Part II (Guest Editor: Vita M. Golubovskaya)]

I would like to thank all the authors for their excellent contributions to the Focal Adhesion Kinase Signaling issue. I would also like to thank the journal for the invitation and the editorial staff for their expert help in the preparation of the second part of this issue. Focal Adhesion Kinase (FAK) is a 125 kDa protein that is localized at the focal adhesions. It plays a significant role in adhesion, motility, invasion, survival, proliferation, metastasis, angiogenesis and lymphangiogenesis. Focal Adhesion Kinase is a cytoplasmic protein, but recently has been found to have novel functions in the nucleus. The authors of this issue summarize the novel functions and interactions and cross-talk of Focal Adhesion Kinase with other signaling pathways in cancer cells. This issue is interesting and important for the development of new therapies, as it summarizes data and literature in different model organisms, such as Xenopus laevis, Drosophila melanogaster, Homo sapiens and describes FAK signaling in different types of cancer: colon, esophageal, prostate, breast, pancreatic and lung cancers. This issue also discusses the interaction of FAK with important signaling pathways such as p53, IGF-1R, AKT, ERK1/2, HA/HAS3, WNT3, Pax-5 and Lgl/Hugl pathways in different cancer cells. The review of Vita M. Golubovskaya and William G. Cance summarizes the data on the nuclear function of FAK and the novel interaction of FAK with p53 that the authors first discovered in 2005 (Golubovskaya et al., JBC, 2005). The authors discuss the fact that FAK can inhibit the transcriptional activity of p53 through direct interaction with p53 protein, and that p53 can block the transcription of FAK through binding to the FAK promoter. There is feed forward loop regulation between FAK and p53 pathways and balance to regulate survival of cancer cells. The authors discuss the fact that targeting this interaction can be very important for cancer therapy. The paper of Teng et al. demonstrates data that inhibition of the HAS3 pathway in colon cancer decreased colon cancer growth by increasing apoptosis. It is known that hyaluronan (high molecular cell surface glycisaminoglycan) and hyaluronan syntases have been implicated in cancer growth. It is also known that FAK and HA signaling inter crossed and HA can stimulate FAK signaling. The authors recently found that FAK and HA pathways interact in colon cancer. Also, Focal Adhesion Kinase is known to be overexpressed in colon cancer. The authors show that inhibition of HAS signaling increased apoptosis and blocked HCT116 colon cancer tumor growth. The authors discuss the intersection of HA-CD44 and FAK pathways in colon cancer and inhibitors of the HA pathway for colorectal therapy in clinical trials. The combination of FAK and HAS inhibitors would be interesting to test in future studies. The review of Figel and Gelman is focused on the role of Focal Adhesion Kinase in prostate cancer. The authors discuss the kinase-dependent function of FAK in prostate cancer, summarize data on its expression in vitro and in vivo models and discuss inhibitors of FAK. The paper of Ucar et al. demonstrates data on novel inhibitor of FAK and IGF-1R interaction in esophageal cancer. The authors used a computer modeling approach to target FAK and IGF-1R interaction and found one small molecule that dose-dependently disrupted this interaction, decreased down-stream AKT and ERK1/2 pathways and blocked esophageal tumor growth in vivo. The authors discuss the fact that targeting FAK and IGF-1R can. The review of Fonar and Frank summarizes the data on a novel pathway and crossing of FAK and WNT pathways in the development cancer. The authors discuss their novel data on Xenopus laevis, where depletion of FAK protein eliminated WNT3a expression in the neural plate. The authors discuss the fact that in the mouse intestine FAK activity was induced down-stream of WNT, which was critical for tumor genesis. The authors discuss FAK and WNT interactions in lung, breast, pancreatic, and other cancer types.....