Aberrant TERT expression: linking chronic inflammation to hepatocellular carcinoma^†

Area of Science:

• Cellular Biology
• Oncology
• Molecular Biology

Background:

• Telomerase reverse transcriptase (TERT) is crucial for telomere maintenance and genomic stability.
• TERT also has non-canonical roles in cell proliferation, survival, DNA damage response, and metabolism.
• TERT is upregulated in over 80% of hepatocellular carcinoma (HCC) cases, indicating its significance in liver cancer.

Purpose of the Study:

• To elucidate the precise mechanisms by which TERT contributes to hepatocellular carcinoma (HCC) initiation and progression.
• To investigate the role of TERT in inflammation-driven hepatocarcinogenesis.

Main Methods:

• Utilized the Alb-Cre;TertTg mouse model for studying TERT's role in hepatocarcinogenesis.
• Analyzed clinical HCC samples to validate findings.
• Examined the impact of TERT on NF-κB promoter activity and p21 ubiquitination.

Main Results:

• TERT promotes cell cycle progression and hepatocarcinogenesis.
• TERT enhances NF-κB promoter activity and facilitates p21 ubiquitination.
• Absence of functional p53 accelerates liver tumor development in TERT transgenic mice.

Conclusions:

• TERT plays a critical role in inflammation-driven hepatocarcinogenesis.
• TERT's mechanisms involve enhancing NF-κB activity and p21 ubiquitination.
• TERT is a key driver of liver cancer progression.