ERRFI1 induces apoptosis of hepatocellular carcinoma cells in response to tryptophan deficiency

Abstract

Tryptophan metabolism is an essential regulator of tumor immune evasion. However, the effect of tryptophan metabolism on cancer cells remains largely unknown. Here, we find that tumor cells have distinct responses to tryptophan deficiency in terms of cell growth, no matter hepatocellular carcinoma (HCC) cells, lung cancer cells, or breast cancer cells. Further study shows that ERRFI1 is upregulated in sensitive HCC cells, but not in resistant HCC cells, in response to tryptophan deficiency, and ERRFI1 expression level positively correlates with HCC patient overall survival. ERRFI1 knockdown recovers tryptophan deficiency-suppressed cell growth of sensitive HCC cells. In contrast, ERRFI1 overexpression sensitizes resistant HCC cells to tryptophan deficiency. Moreover, ERRFI1 induces apoptosis by binding PDCD2 in HCC cells, PDCD2 knockdown decreases the ERRFI1-induced apoptosis in HCC cells. Thus, we conclude that ERRFI1-induced apoptosis increases the sensitivity of HCC cells to tryptophan deficiency and ERRFI1 interacts with PDCD2 to induce apoptosis in HCC cells.

A new acidic microenvironment related lncRNA signature predicts the prognosis of liver cancer patients

“…Khamis et al reported that cytochrome P450-2D6 enzyme (CYP2D6) might act as a putative marker in LC health inequalities, with a negative correlation to IL6 proclaimed a complex relation between CYP2D6 and inflammation in the ethnic differences observed in Asian Americans and Caucasian Americans LC individuals (28). (32). Thomas et al identified that increased primary bile acids and taurine over glycine-conjugated ratios were highly correlated with HCC risk, while the secondary bile acids over primary bile acids ratios were inversely correlated with HCC risk (33).…”

“…Cui et al. concluded that ERRFI1-induced apoptosis rendered HCC cells more sensitive to tryptophan shortage, and ERRFI1 interacted with PDCD2 to cause apoptosis in HCC cells ( 32 ). Thomas et al.…”

Comprehensive serum metabolomics and network analysis to reveal the mechanism of gypenosides in treating lung cancer and enhancing the pharmacological effects of cisplatin

“…Studies have shown that tryptophan metabolism is significantly increased in tumors, which can promote tumorigenesis and immune escape ( Cui et al, 2021 ). It is reported that there is a correlation between glycerophospholipids metabolic disorder and tumorigenesis, and glycerophospholipids are associated with tumorigenesis and development, glycerophosphatides are the main components of biofilms ( Chen et al, 2022 ), glycerolphospholipid metabolism is the most critical pathway associated with NSCLC ( Wu et al, 2020 ).…”

ERRFI1 exacerbates hepatic ischemia reperfusion injury by promoting hepatocyte apoptosis and ferroptosis in a GRB2-dependent manner

“…Previous studies have demonstrated that ERRFI1 serves as a tumor suppressor gene with reduced expression in a variety of human cancers, and loss of function of this protein contributes to cancer development (Zhang et al 2007 ; Amatschek et al 2004 ; Cui et al 2022 ). For example, ERRFI1 induces apoptosis of hepatocellular carcinoma cells (Cui et al 2021 ; Qu et al 2022 ). In addition to cancer, ERRFI1 has been implicated in many pathological situations.…”