Dataset Information


IQGAP1 Scaffold-Kinase Interaction Blockade Selectively Targets Ras-MAP Kinase Driven Tumors

ABSTRACT: MAPK scaffolds, such as IQGAP1, assemble pathway kinases together to effect signal transmission and disrupting scaffold function therefore offers a potentially orthogonal approach to MAPK cascade inhibition. Consistent with this possibility, we observed an IQGAP1 requirement in Ras-driven tumorigenesis in mouse and human tissue. Delivery of the IQGAP1 WW peptide sequence that mediates Erk1/4 binding, moreover, disrupted IQGAP1-Erk1/2 interactions, abolished Ras/Raf-driven tumorigenesis, bypassed acquired resistance to the B-Raf inhibitor vemurafinib (PLX- 4032), and acts as a systemically deliverable therapeutic to significantly increase lifespan of tumor bearing mice. Scaffold-kinase interaction blockade (SKIB) acts by a mechanism distinct from direct kinase inhibition and represents a strategy to target over-active oncogenic kinase cascades in cancer. Gene expression profiling: Fragmented cRNA was hybridized to the Mouse Gene 1.0 ST Array (Affymetrix). Iqgap1 wild-type and Iqgap1 knockout mouse treated with topical 4OHT for 0 days and 6 days days are compared.

ORGANISM(S): Mus musculus  

SUBMITTER: Julien Sage   Paul A Khavari  Pawel K Mazur  Jiajing Zhang  Brian J Zarnegar  Katherine L Jameson  Ashley M Zehnder  Kun Qu 

PROVIDER: E-GEOD-44967 | ArrayExpress | 2013-04-01



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