Figure 3
From: An mTOR feedback loop mediates the ‘flare’ (‘rebound’) response to MET tyrosine kinase inhibition
AKT/MTOR axis inactivates PTP1B and drives the flare effect. (A) EBC1 and HS746T cell lines were treated ON with JNJ-605 or DMSO (VEH). Following inhibitor withdrawal (WO), cells were harvested at the indicated time points (h). Total cellular lysates from the samples shown on top were immunoblotted, as indicated on the left. Black-edged rectangles delineate the blot. The dashed red vertical line highlights the separation between cell lines for clarity. (B) Correlation heatmap showing the relationship between mTOR activation and PTP1B phosphorylation in cancer patients (TCGA data, N = 42 patients). The colour code represents the Pearson correlation score. (C) Cells were treated ON with JNJ-605 or DMSO (VEH). After JNJ-605 WO, 1uM of MK-2206 (AKTi), 1uM of JA-AB2-011 (mTORC2i), 0.1uM of rapamycin (mTORC1i), or 1uM of Temsirolimus (mTORC1/2i) were added in the culture medium. Cells were lysed for immunoblotting 48 h later. Black-edged rectangles delineate the blot.
