Details

Autor(en) / Beteiligte

• Chang, Chih-Peng
• Su, Yu-Chi
• Lee, Pei-Huan
• Lei, Huan-Yao

Titel

Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation

Ist Teil von

• Autophagy, 2013-04, Vol.9 (4), p.619-621

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2013

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• Tumor-associated macrophages (TAMs) have been linked to promoting tumor progression by stimulating angiogenesis, cell growth and inflammation. NFKB activity in TAMs may mediate inflammation-associated tumor formation. However, most isolated TAMs from established tumors express a M2 phenotype with less NFKB activation and show a strong immunosuppressive phenomenon. How tumors affect the dynamic of NFKB activity in TAMs, and hence maintain their pro-tumor M2 phenotype is still poorly understood. We recently found that hepatoma-derived toll-like receptor 2 (TLR2)-related ligands are capable of stimulating M2 macrophage differentiation via controlling NFKB RELA/p65 protein homeostasis by selective autophagy. TLR2 signal induces NFKB RELA cytosolic ubiquitination and leads to its degradation by SQSTM1/p62-mediated autophagy. Inhibition of autophagy will rescue NFKB activity and shape the phenotype of hepatoma-polarized M2 macrophages. This suggests that autophagy might play a role in manipulating TAM functions and tumor-associated immune responses. Our study also demonstrates that autophagy can directly control a transcriptional factor in addition to its regulatory molecules. This finding uncovers a new role of autophagy in controlling cellular functions.