AKT Signaling in Regulating Angiogenesis
Pp. 22-50 (29)
Bing-Hua Jiang and Ling-Zhi Liu
AKT is a central signaling molecule in regulating cell survival, proliferation,
tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as
PI3K, PTEN, and Ras are commonly mutated in many human cancers. Some miRNAs are
also involved in regulating PI3K/AKT signaling pathway. Recently it is found that AKT
plays an important role in regulating normal vascularization and pathological angiogenesis.
Angiogenesis is required for tumor growth and metastasis when tumor reaches more than 1
mm in diameter. This review focuses on the role and potential mechanism of AKT
signaling in regulating angiogenesis. Recent studies have shown that AKT activation is
necessary and sufficient to regulate VEGF and HIF-1α expression in human cancer cells.
VEGF and HIF-1α are potent inducers of angiogenesis. It was found that AKT activation
induces VEGF and HIF-1α expression through its two downstream molecules HDM2 and
p70S6K1. On the other hand, AKT transmits the upstream signals from growth factors,
cytokines, heavy metals, and oncogenes for regulating VEGF and HIF-1α expression in
human cancer cells. AKT activation and VEGF expression can be inhibited by different
natural products used for cancer prevention. Thus, inhibition of AKT and its downstream
targets offers a new approach for targeting angiogenesis, which could be important for the
development of new cancer therapeutics in the future.
AKT, VEGF, HIF-1, tumor growth, vascularization, and angiogenesis.
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107