PKB/Akt-dependent regulation of cell motility.
The prosurvival activity of phosphoinositide 3 kinase (PI3K)/Akt (also known as protein kinase B, PKB) pathway has been investigated in great detail in human physiology and disease. Accumulating evidence is emerging that this signaling axis also actively engages with the migratory process in motile cells, including metastatic cancer cells. Interference with the role of PI3K/Akt-mediated cell motility impairs cellular development and attenuates malignant progression of cancer metastasis. Because metastasis is responsible for 90% of mortality in cancer patients, the acceleration of cancer cell spreading observed in association with hyperactivation of the PI3K pathway, triggered for example by chemotherapy/radiotherapy in the clinic, has heightened awareness of the conflict between "good drugs" and unfavorable effects. Here, we discuss recent studies on PI3K/Akt-regulated cell motility in both physiological and pathological settings, with the aim of a better understanding of how activities of the PI3K/Akt axis initiate and transmit "migratory signals" that stimulate cell movement. We focus in particular on its direct influence on cell migration and invasion, epithelial-mesenchymal transition, and cancer metastasis.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland. gongda.xue@fmi.ch
Gongda
G
Xue
Brian A
BA
Hemmings
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020690:GTPase-Activating Proteins; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000187:drug effects; D036081:Receptors, Eph Family / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014183:Transplantation, Heterologous
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000199:Actins; D020690:GTPase-Activating Proteins; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D036081:Receptors, Eph Family; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases; C507017:ACAP1 protein, human