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Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy
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Autophagy regulates tumor growth and metastasis

Lei Qiang1, Baozhong Zhao1, Mei Ming1

  • 1Department of Medicine, Section of Dermatology, University of Chicago, Chicago, IL, USA.

Biorxiv : the Preprint Server for Biology
|November 14, 2023
PubMed

Insights

Autophagy inhibition stabilizes Twist1 via p62, promoting cancer cell proliferation and metastasis. This study reveals the autophagy/p62/Twist1 pathway as crucial for tumor development and spread.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • The role of autophagy in cancer progression, including tumorigenesis and metastasis, requires further elucidation.
  • Understanding the molecular mechanisms governing tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) is critical for developing targeted therapies.

Approach:

  • Investigated the impact of autophagy inhibition on the stability of the transcription factor Twist1.
  • Utilized molecular biology techniques to examine the interaction between Sequestosome-1 (SQSTM1, also known as p62) and Twist1.
  • Assessed the effect of the autophagy/p62/Twist1 axis on tumor growth and metastasis in preclinical models.

Key Points:

  • Autophagy inhibition leads to Twist1 stabilization through SQSTM1/p62, enhancing tumor cell proliferation, migration, and EMT.
  • SQSTM1/p62 interacts with ubiquitinated Twist1, preventing its proteasomal degradation.
  • Lysine 175 of Twist1 is essential for its ubiquitination, degradation, and interaction with SQSTM1/p62.
  • SQSTM1/p62 promotes tumor growth and metastasis in squamous skin cancer and melanoma models expressing Twist1.

Conclusions:

  • Identified Twist1 as a key downstream effector of autophagy in cancer.
  • Established the autophagy/p62/Twist1 signaling axis as a critical regulator of cancer development and metastasis.
  • Suggests therapeutic potential in targeting this pathway for cancer treatment.

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