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J Cell Physiol. 2013 Jan;228(1):21-4. doi: 10.1002/jcp.24115.

AKT as locus of cancer angiogenic robustness and fragility.

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1
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. zradisavljevic@rics.bwh.harvard.edu

Abstract

Angiogenesis get full robustness in metastatic cancer, relapsed leukemia or lymphoma when complex positive feedback loop signaling systems become integrative. A cancer hypoxic microenvironment generates positive loops inducing formation of the vascular functional shunts. AKT is an upstream angiogenic locus of integrative robustness and fragility activated by the positive loops. AKT controls two downstream nodes the mTOR and NOS in nodal organization of the signaling genes. AKT phosphorylation is regulated by a balance of an oxidant/antioxidant. Targeting AKT locus represents new principle to control integrative angiogenic robustness by the locus chemotherapy.

PMID:
22585603
DOI:
10.1002/jcp.24115
[Indexed for MEDLINE]
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