Synthetic Lethal Screen of an EGFR-Centered Network to Improve Targeted Therapies

Igor Astsaturov, Vladimir Ratushny, Anna Sukhanova, Margret B. Einarson, Tetyana Bagnyukova, Yan Zhou, Karthik Devarajan, Joshua S. Silverman, Nadezhda Tikhmyanova, Natalya Skobeleva, Anna Pecherskaya, Rochelle E. Nasto, Catherine Sharma, Sandra A. Jablonski, Ilya G. Serebriiskii,* Louis M. Weiner,* Erica A. Golemis*

*To whom correspondence should be addressed. E-mail: weinerl{at}georgetown.edu (L.M.W.); ea_golemis{at}fccc.edu (E.A.G.); ig_serebriiskii{at}fccc.edu (I.G.S.)

This PDF file includes:

• Fig. S1. Optimization assays to establish critical assay parameters for screening.
• Fig. S2. Schematic of screen strategy and hit selection.
• Fig. S3. Efficiency of gene knockdown for a representative set of siRNAs used.
• Fig. S4. Representative Western blots showing the overall abundance and phosphorylation status of EGFR pathway members in A431 cells transfected with siRNAs targeting the indicated genes.
• Fig. S5. Synergistic in vitro activity of signaling inhibitors.
• Fig. S6. Phosphoprotein changes with signaling inhibitors.
• Fig. S7. PHA-680632 and erlotinib combine to reduce AKT phosphorylation.
• Fig. S8. Expression profile of hits in cell lines.
• Fig. S9. Expression profile of hits in Oncomine.
• Tables S1 and S2 legend

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Other Supplementary Material for this manuscript includes the following:

• Table S1. List of genes included in the targeted library, including official gene name, gene symbol, and reasons for inclusion in the library (Microsoft Excel format).


• Table S2. Sequences of the siRNAs for the 61 validated target genes (Microsoft Excel format).

© 2010 American Association for the Advancement of Science