Unexpectedly, we found that EGFR signaling, one non-canonical pathway bears the capacity to activate β-catenin via AKT/GSK3β (Hofmockel et al., 1997; Hashmi et al., 2018; Ge et al., 2020), was significantly enriched in the ccRCC patients with low ATF3 expression (Figure 6A), suggesting loss of ATF3 may activate β-catenin via EGFR/AKT/GSK3β signaling. This evidence concerns the gene GSK3B and nonpapillary renal cell carcinoma.