AKT as locus of cancer positive feedback loops and extreme robustness

Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston Massachusetts 02115. .
Journal of Cellular Physiology (Impact Factor: 3.87). 03/2013; 228(3). DOI: 10.1002/jcp.24167
Source: PubMed

ABSTRACT A positive feedback loops induce extreme robustness in metastatic cancer, relapsed leukemia, myeloma or lymphoma. The loops are generated by the signaling interactome networks of auocrine and paracrine elements from cancer hypoxic microenvironment. The elements of the networks are signaling proteins synthesized in hypoxic microenvironment such as the VEGF, HIF-1α, HGF, and molecule H(2) O(2) . The signals from upstream or rebound downstream pathways are amplified by the short or wide positive feedback loops, hyperstimulating AKT inducing cancer extreme robustness. Targeting the phosphorylated AKT locus by an oxidant/antioxidant modulation induces collapse of positive feedback loops and establishment of negative feedback loops leading to stability of the system and disappearance of cancer extreme robustness. This is a new principle for the conversion of cancer positive loops into negative feedback loops by the locus chemotherapy. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.

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