Figure S4 from Tumor Intrinsic Efficacy by SHP2 and RTK Inhibitors in KRAS-Mutant Cancers
Year: 2023
Type: other
Abstract: (A) Immunoblot of p-RSK3 and qPCR for DUSP6 from MIA PaCa-2 xenografts collected 3 hours after the last dose from Fig 5C. (B) Immunoblot for the designated proteins from MIA PaCa-2 cells grown in 2D, 3D and from in vivo xenografts without compound treatment. Protein loading amount was normalized and verified by tubulin loading control. Each separate column represents an individual treated tumor. (C) Dependency of MET by DRIVE pooled shRNA screen (y axis, ATARIS Quantile score of less than -0.5 indicates a significant effect) and expression of HGF (x-axis) by RNAseq in pancreatic cancer cell lines in CCLE (n=21). (D) Immunoblot of p-RSK3 and qPCR for DUSP6 from KP4 xenografts collected 3 hours after the last dose from Fig 5E. Protein loading amount was normalized and verified by tubulin loading control. Each separate column represents an individual treated tumor (E) Immunoblot for the designated proteins from KP4 cells grown in 2D, 3D and from in vivo xenografts without compound treatment (F) Schematic of RTK-SHP2 signaling highlighting that SHP2 acts downstream of one or more activated RTKs to elicit downstream signaling in KRAS mutant and also additional SHP2-specific, non-MAPK signaling. SHP2 inhibition by SHP099 can serve as a surrogate for cancers where KRAS mutant cancers are dependent on upstream RTKs.
Authors: Huai-Xiang Hao, Hongyun Wang, Chen Liu, Steven Kovats, Roberto Velazquez, Hengyu Lu, Bhavesh Pant, Matthew Shirley, Matthew J. Meyer, Minying Pu, Joanne Lim, Michael Fleming, LeighAnn Alexander, Ali Farsidjani, Matthew J. LaMarche, Susan Moody, Serena J. Silver, Giordano Caponigro, Darrin D. Stuart, Tinya J. Abrams, Peter S. Hammerman, Juliet Williams, Jeffrey A. Engelman, Silvia Goldoni, Morvarid Mohseni
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4362482023