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TRAF6 regulates autophagy and apoptosis of melanoma cells through c-Jun/ATG16L2 signaling pathway

Yeye Guo1,2,3,4,5, Xu Zhang1,2,3,4,5, Jie Li1,2,3,4,5

  • 1Department of Dermatology Xiangya Hospital Central South University Changsha China.

Medcomm
|July 24, 2023
PubMed

Insights

Targeting tumor necrosis factor receptor-associated factor 6 (TRAF6) in melanoma induces apoptosis and autophagy. Inhibiting TRAF6 with cinchonine suppresses melanoma growth by activating the TRAF6/c-Jun/ATG16L2 pathway, offering a new therapeutic strategy.

Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • Autophagy and apoptosis are critical for cellular homeostasis; their dysregulation contributes to cancer development.
  • Tumor necrosis factor receptor-associated factor 6 (TRAF6) is overexpressed in melanoma and promotes its malignant phenotype.
  • The specific roles of TRAF6 in melanoma cell autophagy and apoptosis were previously unclear.

Purpose of the Study:

  • To investigate the role of TRAF6 in regulating autophagy and apoptosis in melanoma cells.
  • To elucidate the molecular mechanisms underlying TRAF6-mediated regulation of these processes.
  • To evaluate the therapeutic potential of targeting TRAF6 in melanoma.

Main Methods:

  • Gene knockdown of TRAF6 and autophagy related 16 like 2 (ATG16L2) in melanoma cells.
  • Transcriptomic analysis and real-time PCR to assess gene expression.
  • Mechanism studies involving c-Jun and TRAF6 inhibition using cinchonine.

Main Results:

  • TRAF6 knockdown induced both apoptosis and autophagy in melanoma cells.
  • TRAF6 deficiency led to reduced ATG16L2 expression, which in turn increased autophagy and apoptosis.
  • TRAF6 regulates ATG16L2 expression via the c-Jun pathway.
  • Cinchonine, a TRAF6 inhibitor, suppressed melanoma cell growth by inducing apoptosis and autophagy.

Conclusions:

  • TRAF6 plays a crucial role in controlling autophagy and apoptosis in melanoma.
  • The TRAF6/c-Jun/ATG16L2 signaling pathway is a key mechanism in melanoma progression.
  • Targeting TRAF6 represents a promising therapeutic strategy for melanoma treatment.
Keywords:
ATG16L2TRAF6apoptosisautophagyc‐Junmelanoma

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