ESR2 and colorectal carcinoma: In Figure 2, we propose that an inverse relationship exists between ERβ and PTEN/PI3K/AKT which modulates ASNS expression and influences CRC progression; PTEN can inhibit PI3K/AKT signaling, and loss of PTEN expression co-occurs with KRAS and PIK3CA mutations (De Roock et al., 2011), enhanced PI3K/AKT signaling can induce ERβ ubiquitination and degradation (Zhou and Liu, 2020).