Intracellular signaling in tumor and endothelial cells: The expected and, yet again, the unexpected.
In this issue of Cancer Cell, Phung and coworkers demonstrate that sustained endothelial activation of Akt by expression of constitutively activated Akt1 (myrAkt1) leads to blood vessels that essentially recapitulate the complex structural and functional abnormalities of tumor vessels. The authors provide evidence that rapamycin inhibition of PI3K/Akt/mTOR signaling in endothelial cells (ECs), by either reducing Akt activity or blocking mTOR, reverses the pathologic effects associated with excess VEGF signaling in the tumor vasculature. However, unexpected findings following mTOR inhibition in vivo highlight the seemingly paradoxical and complex effects of rapamycin on various cell types within the tumor microenvironment.
Stoeltzing
Oliver
O
Department of Surgery and Surgical Oncology, University of Regensburg Medical Center, Regensburg 93053, Germany.
Meric-Bernstam
Funda
F
Ellis
Lee M
LM
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation; D011494:Protein Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human