Journal
SCIENTIFIC REPORTS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep17626
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Funding
- National Natural Science Foundation of China [31171885, 31371957]
- Changjiang Scholars and Innovative Research Team in University [IRT_15R16]
- Ph.D. Programs Foundation of Ministry of Education of China [201213 01110006]
- Key Projects in the Hebei Province Science Technology [13226508D]
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Shp2 is a ubiquitously expressed protein tyrosine phosphatase (PTP) related to adult acute myelogenous leukemia and human solid tumors. In this report, we describe identification of a potent Shp2 inhibitor, Fumosorinone (Fumos) from entomogenous fungi, which shows selective inhibition of Shp2 over other tested PTPs. Using a surface plasmon resonance analysis, we further confirmed the physical interaction between Shp2 and Fumos. Fumos inhibits Shp2-dependent activation of the Ras/ERK signal pathway downstream of EGFR, and interrupts EGF-induced Gab1-Shp2 association. As expected, Fumos shows little effects on the Shp2-independent ERK1/2 activation induced by PMA or oncogenic Ras. Furthermore, Fumos down-regulates Src activation, inhibits phosphorylation of Paxillin and prevents tumor cell invasion. These results suggest that Fumos can inhibit Shp2-dependent cell signaling in human cells and has a potential for treatment of Shp2-associated diseases.
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