Axl Receptor Axis: A New Therapeutic Target in Lung Cancer

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Presentation transcript:

Axl Receptor Axis: A New Therapeutic Target in Lung Cancer Pavel A. Levin, MD, PhD, Rolf A. Brekken, PhD, Lauren Averett Byers, MD, John V. Heymach, MD, PhD, David E. Gerber, MD Journal of Thoracic Oncology Volume 11, Issue 8, Pages 1357-1362 (August 2016) DOI: 10.1016/j.jtho.2016.04.015 Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 Axl signaling and regulation. Upper panel: Axl signlaling. (A) Axl signaling includes three well-described pathways: (1) Ras/Raf/MEK/ERK, (2) Elmo1/2/DOCK1/Rac1/Pak, and (3) Gab2/PI3K/Akt. These pathways promote cancer cell proliferation, migration, and survival. (B–F) Patterns of Axl activation, including ligand-dependent activation through interaction with Gas6 (B) and ligand-independent activation either through Axl transcellular homophilic binding and adhesion (C), overexpression (D), interaction with another TAM family member receptor (Tyro3) (E), or heterodimerization with a non-TAM family receptor such as EGFR (F). Lower panel: Axl regulation. Axl synthesis from DNA to mRNA to protein is regulated at each step by transcription factor activation, DNA methylation, RNA interference, and protein folding. Ap1, activated protein 1; Chr 19, chromosome 19; DOCK1, dedicator of cytokinesis 1; EGFR, epithelial growth factor receptor; Elmo 1/2, engulfment and cell motility protein 1 and 2; ERK, extracellular signal regulated kinase; FNIII, fibronectin III; Gab2, GRB2-associated binding protein 2; Gas6, growth arrest-specific 6; Grb2, growth factor receptor-bound protein 2; HIF1, hypoxia-inducible factor 1; HSP90, heat shock protein 90; Ig, immunoglobulin; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; MZF1, myeloid zinc finger 1; PAK, p21 protein-activated kinase; PI3K, phosphoinositide-3 kinase (consists of p85 and p110 subunits); PIP2, phosphatidylinositol (3,4)-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-triphosphate; Rac1, Rho-family small GTP-binding protein 1; SOS, son of sevenless; SP1 and SP3, specificity protein 1 and 3; YAP1, yes-associated protein 1. Journal of Thoracic Oncology 2016 11, 1357-1362DOI: (10.1016/j.jtho.2016.04.015) Copyright © 2016 International Association for the Study of Lung Cancer Terms and Conditions