Figure 4: Functional dissection of mTORC1 and mTORC2 in cell growth and stroma/MCL interaction in acquired IR MCL cells.

(a–c) Treatment with the PI3K/mTOR inhibitors BEZ235 and AZD8055, but not ibrutinib, significantly decreased AKT phosphorylation, β1 expression (a,b), and adhesion to HK stromal cells (c) in IR MCL cells. (d) Rapamycin inhibited mTORC1 activation, but had no effect on AKT activation and β1 expression in IR MCL cells. (e,f) Inhibition of mTORC2 by rictor knockdown using a pool of siRNAs decreased AKT activation, β1 expression and cell adhesion. In contrast, blocking mTOR1 by raptor knockdown with siRNA showed no changes in AKT activation and β1 expression in IR MCL cells. (g) Treatment with AKT inhibitor (AKTi, A674563, for 12 h) significantly attenuated β1 (CD29) expression in IR MCL cells. (h) Diagram of functional regulation of mTORC1 and mTORC2 in proliferation, AKT activation, β1 expression and cell adhesion in IR cells. Results in a–g are representative of at least three independent experiments or means±s.d. from at least three biological replicates. See also Supplementary Figs 4, 8 for full gel scan of the WB.