Autophagy negatively regulates cancer cell proliferation via selectively targeting VPRBP

Area of Science:

• Cellular Biology
• Cancer Research
• Molecular Mechanisms of Autophagy

Background:

• Autophagy plays a dual role in cancer, regulating both bulk degradation and selective targeting of signaling proteins.
• LC3B (light-chain 3B) is a key receptor protein mediating substrate sequestration into autophagosomes during autophagy.

Purpose of the Study:

• To identify novel autophagic substrates and LC3B-binding partners in cancer cells.
• To investigate the role of viral protein R-binding protein (VPRBP) in autophagy-mediated protein degradation and its clinical relevance in lung cancer.

Main Methods:

• Screening of LC3B-binding partners using GST-LC3B pull-down assays combined with LC-MS/MS.
• Co-immunoprecipitation assays to confirm protein complex formation.
• Autophagy induction and inhibition experiments (BFA1, ATG5-knockdown) in lung and esophageal cancer cell lines.
• Immunohistochemical analysis of human non-small cell lung cancer (NSCLC) tissues.

Main Results:

• VPRBP was identified as a novel LC3B-binding protein and an autophagic substrate in NCI-H1975 and KYSE30 cancer cell lines.
• VPRBP forms a complex with LC3B and p62, and its degradation is dependent on autophagy.
• Autophagy induction promotes VPRBP-LC3/p62 interaction.
• In human NSCLC tissues, VPRBP expression positively correlates with p62 and negatively with LC3B.
• VPRBP and p62 expression are associated with poor prognosis in lung adenocarcinoma (ADC).

Conclusions:

• VPRBP is a novel substrate of selective autophagy regulated by LC3B.
• The VPRBP-LC3B-p62 axis is implicated in cancer progression and serves as a potential prognostic biomarker in NSCLC.
• Targeting VPRBP degradation through autophagy modulation may offer therapeutic strategies for lung cancer.