PDC and neoplasm: Interestingly, we identified the HIF signaling pathway as a pivotal upstream regulator of the GPx2 KD tumor response, as shown by activation of HIF1α (Z-score = 2.033) and HIF1β (ARNT) (Z-score = 3.065) that was interestingly accompanied by inhibition of PHD (EGLN) (Z-score = −2.455) (SI Appendix, Fig. S7 E–G), a destabilizer of HIF1α.