Tissue factor promotes HCC carcinogenesis by inhibiting BCL2-dependent autophagy

Area of Science:

• Oncology
• Cell Biology
• Molecular Medicine

Background:

• Tissue factor (TF) is a known prognostic marker in hepatocellular carcinoma (HCC).
• TF influences BCL2 expression, a key regulator of autophagy.
• Understanding the interplay between TF, BCL2, and autophagy is crucial for HCC treatment.

Purpose of the Study:

• To investigate the role of BCL2-dependent autophagy in TF-mediated HCC carcinogenesis.
• To elucidate the molecular mechanisms by which TF regulates autophagy and cell survival in HCC.

Main Methods:

• Gene overexpression and silencing assays were used to study TF function in HCC cells.
• Pharmacological autophagy inhibitors (3-MA, spautin-1) were combined with TF manipulation.
• In vivo tumorigenicity was assessed using xenograft models.

Main Results:

• Overexpressed TF increased BCL2, inhibited autophagy (reduced LC3 conversion, increased p62, fewer autophagosomes), and promoted HCC cell survival.
• TF silencing decreased BCL2, enhanced autophagy, and reduced cell survival.
• TF knockdown led to Beclin1 dissociation from the BCL2-Beclin1 complex.
• Autophagy inhibition reversed the effects of TF knockdown on cell survival and tumor growth.

Conclusions:

• TF promotes HCC tumorigenesis by inhibiting autophagy-related cell death.
• This inhibition occurs via enhanced BCL2 expression, which suppresses autophagy.
• Targeting the TF-BCL2-autophagy pathway may offer therapeutic strategies for HCC.