CES3 promotes NSCLC progression via lipid metabolic reprogramming regulated by TFAP2A

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Metabolic reprogramming is a hallmark of non-small cell lung cancer (NSCLC), contributing to therapeutic resistance.
• Dysregulated lipid metabolism in NSCLC presents opportunities for identifying novel biomarkers and therapeutic targets.

Purpose of the Study:

• To investigate the role of carboxylesterase 3 (CES3) in NSCLC progression and its relationship with transcription factor AP-2α (TFAP2A).
• To explore the potential of targeting the TFAP2A/CES3 axis as a therapeutic strategy for NSCLC.

Main Methods:

• RNA next-generation sequencing was performed on 25 paired NSCLC and adjacent normal tissues.
• Functional studies involved knockdown and overexpression of CES3 and TFAP2A in NSCLC cells.
• Analysis included cell proliferation, invasion assays, and lipid accumulation assessments.

Main Results:

• Carboxylesterase 3 (CES3) was found to be upregulated in NSCLC tissues.
• CES3 knockdown inhibited NSCLC cell proliferation and invasion while promoting lipid accumulation.
• Transcription factor AP-2α (TFAP2A) was upregulated in NSCLC, correlated with poor outcomes, and regulated CES3 levels.
• TFAP2A inhibition suppressed NSCLC progression and increased lipid accumulation, effects reversed by CES3 overexpression.

Conclusions:

• TFAP2A dysregulation drives NSCLC tumorigenesis through CES3 overexpression.
• The TFAP2A/CES3 axis represents a promising therapeutic target for non-small cell lung cancer.