Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation

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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)619-621
Number of pages3
JournalAutophagy
Volume9
Issue number4
DOIs
Publication statusPublished - 2013 Jan 1

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Autophagy
Hepatocellular Carcinoma
Macrophages
Neoplasms
Toll-Like Receptor 2
Phenotype
Inflammation
Ubiquitination
Immunosuppressive Agents
Homeostasis
Ligands

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Chang, Chih-Peng ; Su, Yu Chi ; Lee, Pei Huan ; Lei, Huan Yao. / Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation. In: Autophagy. 2013 ; Vol. 9, No. 4. pp. 619-621.
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Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation. / Chang, Chih-Peng; Su, Yu Chi; Lee, Pei Huan; Lei, Huan Yao.

In: Autophagy, Vol. 9, No. 4, 01.01.2013, p. 619-621.

Research output: Contribution to journalArticle

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