Basic fibroblast growth factor in medulloblastoma [Neurosurgery Wiki]

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====== Basic fibroblast growth factor in medulloblastoma ======

Basic [[fibroblast growth factor]] (bFGF) promotes [[medulloblastoma]] (MB) [[tumor cell]] invasion through [[Fibroblast growth factor receptor]]  (FGFR) in vitro and that blockade of [[FGFR]] represses [[brain tissue]] [[infiltration]] [[in vivo]]. Transforming growth factor Beta ([[TGF]]-β) regulates pro-migratory [[bFGF]] function in a context-dependent manner. Under low [[bFGF]], the non-canonical TGF-β [[pathway]] causes [[ROCK]] activation and cortical [[translocation]] of [[ERK]]1/2, which antagonizes [[FGFR]] signaling by inactivating [[FGFR substrate 2]] ([[FRS2]]), and promotes a contractile, non-motile [[phenotype]]. Under high [[bFGF]], negative-[[feedback]] regulation of FRS2 by bFGF-induced ERK1/2 causes repression of the FGFR pathway. Under these conditions, TGF-β counters inactivation of FRS2 and restores pro-migratory signaling. These findings pinpoint coincidence detection of bFGF and TGF-β signaling by FRS2 as a mechanism that controls tumor cell invasion. Thus, targeting FRS2 represents an emerging strategy to abrogate aberrant FGFR signaling
((Santhana Kumar K, Neve A, Guerreiro Stucklin AS, Kuzan-Fischer CM, Rushing EJ,
Taylor MD, Tripolitsioti D, Behrmann L, Kirschenbaum D, Grotzer MA, Baumgartner
M. TGF-β Determines the Pro-migratory Potential of bFGF Signaling in
Medulloblastoma. Cell Rep. 2018 Jun 26;23(13):3798-3812.e8. doi:
10.1016/j.celrep.2018.05.083. PubMed PMID: 29949765.
)).