ERα down-regulates carbohydrate responsive element binding protein and decreases aerobic glycolysis in liver cancer...

Area of Science:

• Oncology
• Molecular Biology
• Endocrinology

Background:

• Deregulated metabolism is a hallmark of hepatocellular carcinoma (HCC).
• Sex hormone receptor signaling contributes to gender disparities in HCC pathogenesis.
• Estrogen receptor (ER) is implicated in reducing liver cancer incidence, but its metabolic regulatory mechanisms in tumor cells are unclear.

Purpose of the Study:

• To investigate the role of ERα in regulating metabolic alterations in liver tumor cells.
• To elucidate the interaction between ERα and carbohydrate responsive element binding protein (ChREBP) in HCC.
• To confirm ERα's function in suppressing aerobic glycolysis in liver cancer.

Main Methods:

• Investigated ERα overexpression effects with E2 treatment on hepatoma cells.
• Assessed changes in aerobic glycolysis and cell proliferation.
• Utilized co-immunoprecipitation to study ERα and ChREBP interactions.
• Examined the impact on ChREBP transcription and protein degradation.

Main Results:

• ERα overexpression with E2 treatment reduced aerobic glycolysis and proliferation in hepatoma cells.
• ERα modestly downregulated ChREBP transcription and promoted ChREBP degradation.
• ERα interacted with both ChREBP-α and ChREBP-β subtypes.
• ERα decreased ChREBP-α-induced ChREBP-β transcription, without altering ChREBP localization.

Conclusions:

• ERα plays a significant role in suppressing aerobic glycolysis in liver cancer.
• ERα regulates ChREBP protein degradation and influences ChREBP-β transcription.
• ERα and ChREBP-α collaboratively regulate ChREBP-β expression, providing insights into HCC metabolic control.