EGF and bFGF Promote Invasion That Is Modulated by PI3/Akt Kinase and Erk in Vestibular Schwannoma

Abstract

Activation of EGFR and FGFR may promote invasive behavior in VS through ERK and Akt signaling pathways. Further investigation will be necessary to elucidate their potential as useful targets in the treatment of VS.

Curcumin Inhibits TGF-β1-Induced MMP-9 and Invasion through ERK and Smad Signaling in Breast Cancer MDA-MB-231 Cells

“…Reportedly, MMP-9 plays a significant role in breast cancer invasion and metastasis via degrading type IV collagen-rich extracelluar matrix (Chen et al, 2011) , and also be regulated by TGF-β1, epidermal growth factor (EGF), fibroblast growth factor (FGF), Nerve growth factor (NGF), vascular endothelial growth factor (VEGF), etc., which secreted by cancer cells and/or host cells in the tumor microenvironment (Chou et al, 2006;Belotti et al, 2008;Blair et al, 2011). Among those factors, TGF-β1 generated by autocrine and paracrine is high related to malignant tumor (Na et al, 2010).…”

Gene-expression profiling elucidates molecular signaling networks that can be therapeutically targeted in vestibular schwannoma

“…Additionally, our analysis identified several pathways previously characterized and implicated in schwannoma, such as IGF signaling, mTOR signaling, and PI3K signaling. 2,5,[14][15][16] Recent evidence has shown that several central nervous system tumors are characterized by great molecular heterogeneity and different clinical outcomes. 23,24,26,35,39,41 Based on several distinct bioinformatic strategies, our data reveal highly similar gene-expression patterns in a molecularly homogeneous tumor entity.…”

“…The PI3K/AKT/mTOR signaling pathway has been implicated as one the most aberrant signaling pathways in several cancers, including glioblastoma, medulloblastoma, breast, lung, colon and prostate cancers. 42 The Class I PI3Ks catalyze the mitogen-stimulated phosphorylation of phosphatidyl-inositol-4,5-bisphosphate (PtdIns [4,5]P2) to produce PtdIns (3,4,5)P3. This creates docking sites for several signaling proteins containing domains capable of binding to PtdIns(3,4,5)P3 or itself, ultimately leading to AKT and mTORC1 and mTORC2 activation.…”

“…6 Schwann cell-specific knockout of NF2 in mice leads to initiation of schwannomas with similarities to VS in patients with NF2. Mechanistically, loss of NF2 has been linked to aberrant activation of signaling pathways involving cell survival, growth, and proliferation, namely the PI3K/AKT/mTOR 5,15,16,28 and ERK1/2 signaling pathways. 1 It has been reported that loss of NF2 by deletion, mutation, or loss of protein or transcript occurs in 66% to 100% of all sporadic schwannomas.…”

Pathogenesis and management of type 2 neurofibromatosis

“…EGFR is expressed and phospho-activated in both NF2-related and sporadic schwannomas [76,77] and the first report of therapy molecularly targeted towards Merlin's known functions was a retrospective report of the EGFR inhibitor Erlotinib by the Boston group [78]. Eleven patients with progressive VS were offered Erlotinib on a compassionate basis, of whom one discontinued treatment after 2 weeks for toxicity.…”