Fig. 6: Her2 knockout induced suppression of the Her2-Her3-PI3K pathway and recovered sensitivity to sotorasib. | npj Precision Oncology

Fig. 6: Her2 knockout induced suppression of the Her2-Her3-PI3K pathway and recovered sensitivity to sotorasib.

From: Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization

Fig. 6

a Certification of Cas9-mediated Her2 knockout. JC261 cells transduced sgHer2 and established Her2 knockout (KO) cell lines. Cell lysates were collected to perform immunoblotting using the indicated antibodies. b Comparison of KRAS downstream signaling between JC261 parent cells and Her2 KO cells in KRAS-G12C inhibition. Cells were exposed to 1 µM of sotorasib each time; cell lysates were then collected and immunoblotted to detect the indicated antibodies. c Evaluation of GTP-KRAS by Ras pull-down assay. Cell lysates were collected, and Ras pull-down assay was performed to detect GTP-KRAS. d Sensitivity to sotorasib in Her2 KO cells. The cells were treated with each concentration of sotorasib for 6 days. e Sensitivity to trametinib in Her2 KO cells. The cells were treated with each concentration of trametinib for 6 days. Cell viability was calculated by CellTiter-Glo assay, and relative cell viability to nontreatment conditions was calculated. Data were shown as mean ± SD.

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