TEAD4 Activates PCSK9 to Promote Stomach Adenocarcinoma Cell Stemness through Fatty Acid Metabolism

Area of Science:

• Oncology
• Molecular Biology
• Cancer Stem Cell Research

Background:

• Stomach adenocarcinoma (STAD) is a significant health concern.
• Understanding the mechanisms driving STAD stemness is crucial for effective treatment.

Purpose of the Study:

• To investigate the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in regulating the stemness of STAD cells.
• To elucidate the relationship between TEAD4 and PCSK9 in STAD progression.

Main Methods:

• Cell viability and stemness assays (CCK-8, sphere-formation).
• Gene expression analysis (qRT-PCR, Western blot) for PCSK9 and TEAD4.
• Molecular interaction studies (dual-luciferase, ChIP).
• In vivo tumor formation experiments in nude mice.

Main Results:

• PCSK9 and TEAD4 were upregulated in STAD tissues.
• PCSK9 promoted STAD cell proliferation and stemness, partly through fatty acid metabolism (FAM).
• TEAD4 acts upstream of PCSK9, forming a TEAD4/PCSK9 axis that drives STAD tumor growth.

Conclusions:

• The transcription factor TEAD4 activates PCSK9, promoting STAD stemness via FAM.
• The TEAD4/PCSK9 axis is a promising therapeutic target for inhibiting cancer stem cells in STAD.