Mechanisms of Disease: PI3K/AKT Signaling in Gastrointestinal Cancers

Zusammenfassung

Die Phosphoinositol-3-OH-Kinase (PI3K) und die von ihr aktivierte Serin/Threoninkinase Akt, auch als Proteinkinase B bekannt, sind wichtige Effektormoleküle verschiedener Rezeptor-Tyrosinkinasen. In den letzten Jahren häufen sich die Daten über Aberrationen bei Komponenten des PI3K/Akt-Signalwegs in verschiedenen Tumoren. Dieser Übersichtsartikel fasst die wichtigsten Berichte über Effekte des PI3K/Akt-Signalwegs auf Proliferation, Apoptoseresistenz, Angiogenese und Zellmotilität in gastrointestinalen Tumoren zusammen. Ferner werden die Aktivierung von PI3K/Akt durch verschiedene Wachstumsfaktoren, die Modulation von Effektormolekülen durch Akt-induzierte Phosphorylierung sowie neuartige Behandlungsstrategien diskutiert, die eine therapeutische Ausschaltung dieses Signalwegs beinhalten.

Abstract

The lipid kinase phosphoinositide 3-OH kinase (PI3K) and its downstream target Akt, also known as protein kinase B (PKB), are crucial effectors in oncogenic signaling induced by various receptor-tyrosine kinases. In recent years, data are accumulating that PI3K/Akt signaling components are frequently altered in a variety of human malignancies. This review summarizes the major effects of PI3K/Akt signaling on proliferation, survival and resistance to apoptosis, angiogenesis and cell motility in gastrointestinal cancers. In addition, activation of PI3K/Akt by various growth factors, the modulation of downstream targets by Akt-induced phosphorylation as well as novel treatment strategies targeting this pathway in gastrointestinal tumors are discussed.

Schlüsselwörter

Akt - Proteinkinase B - PI-3-Kinase - Gastrointestinale - Tumor - Signalweg - Überleben - Proliferation - Apoptose - Metastase

Key words

Akt - protein kinase B - PI-3 kinase - gastrointestinal - tumor - signaling - survival - proliferation - apoptosis - metastasis

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