Table 2. Upstream factors involved in protein expression responses to KPT-185, AZD-2014, or KPT-185+AZD-2014in MCL cells.
| Upstream Regulator | Activation z-score | P-value | Target molecules in dataset |
|---|---|---|---|
| KPT-185 | |||
| Upregulated | |||
| RICTOR | 3.606 | 5.88E-18 | PSME3, RPL10, RPL10A, RPL23, RPL26, RPL28, RPL4, RPL6, RPL7A, RPS10, RPS2, RPS23, RPS3 |
| TP53 | 1.432 | 8.79E-03 | HMGB2, HSPA8, KPNA2, PSME3, VIM, XPO1 |
| Downregulated | |||
| MYC | −3.719 | 9.94E-12 | EEF2, LGALS1, RPL10, RPL19, RPL23, RPL26, RPL27, RPL35, RPL5, RPL6, RPL7A, RPS23, VIM, XPO1 |
| MYCN | −3.499 | 2.88E-26 | EEF2, LGALS1, RPL10, RPL19, RPL23, RPL26, RPL27, RPL28, RPL35, RPL4, RPL5, RPL6, RPS2, RPS23, RPS3, RPS4X, VIM |
| HRAS | −1.982 | 6.54E-03 | HSPA8, RPS10, RPS3, VIM |
| AZD-2014 | |||
| Downregulated | |||
| HSF1 | −1.387 | 1.17E-06 | CCT2, DNAJA1, HSP90AB1, HSPA8, HSPH1 |
| KPT-185+AZD-2014 | |||
| Upregulated | |||
| TNF | 2.795 | 2.54E-03 | FASN, HMGB1, HSP90AB1, HSPA8, HSPD1, PARP1, RRM1, RRM2, TPT1, VIM |
| INSR | 2.224 | 1.10E-07 | ACAA2, ATP5A1, CFL1, FASN, HSPD1, MDH2, PDCD4, RRM1, RRM2 |
| TP53 | 2.109 | 2.67E-07 | ACAA2, ADH5, FASN, HMGB1, HMGB2, HSP90AB1, HSPA8, HSPD1, KPNA2, MDH2, PSME3, RRM1, RRM2, VIM, XPO1 |
| PTEN | 1.724 | 5.33E-05 | ACAA2, FASN, G3BP1, PARP1, PDCD4, PGK1, RRM1 |
| IFNG | 1.387 | 2.38E-02 | EEF1A1, FASN, HMGB1, HSP90AB1, HSPA8, HSPD1, PSME3 |
| OSM | 1.342 | 6.73E-03 | ADH5, FASN, KRT9, PDCD4, PGK1 |
| Downregulated | |||
| p70S6k | −1.982 | 1.03E-09 | EEF1A1, EEF2, FASN, PDCD4, VIM |
| E2F1 | −1.673 | 1.21E-11 | CCT2, CSDE1, HMGB1, HMGB2, HNRNPD, HSPA8, HSPD1, HSPE1, KRT1, NCL, RRM1, RRM2, VIM |
| EGF | −1.627 | 1.10E-04 | EEF1A1, FASN, NCL, PDCD4, RRM1, RRM2, VIM |
| HSF1 | −1.458 | 2.45E-10 | CCT2, DNAJA1, FASN, HMGB1, HSP90AB1, HSPA8, HSPD1, HSPE1, PGK1 |
| MYCN | −1.387 | 7.63E-15 | EEF1A1, EEF1G, EEF2, EIF4A1, HSP90AB1, HSPD1, NCL, RPL4, RPL6, RPS3A, RPS7, TPI1, VIM |
Data were analyzed by Ingenuity Pathway Analysis (IPA) based on the proteins whose expression was consistently altered after indicated treatment in Jeko-1, Z138, JVM2, and MINO cells (Supplementary Table 1).