Details

Autor(en) / Beteiligte

• Ma, Zikun
• Li, Zhiyong
• Mao, Yize
• Ye, Jingwei
• Liu, Zefu
• Wang, Yuzhao
• Wei, Chen
• Cui, Jun
• Liu, Zhuowei
• Liang, Xiaoyu

Titel

AhR diminishes the efficacy of chemotherapy via suppressing STING dependent type-I interferon in bladder cancer

Ist Teil von

• Nature communications, 2023-09, Vol.14 (1), p.5415-5415, Article 5415

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract The induction of type-I interferons (IFN-Is) is important for the efficacy of chemotherapy. By investigating the role of amino acids in regulation of IFN-I production under chemo-drug treatment in bladder cancer (BC) cells, we find an inherent AhR-dependent negative feedback to restrain STING signaling and IFN-I production. Mechanistically, in a ligand dependent manner, AhR bridges STING and CUL4B/RBX1 E3 ligase complex, facilitating STING degradation through ubiquitin-proteasome pathway. Inhibition of AhR increases STING levels and reduces tumor growth under cisplatin or STING agonist treatment. Endogenous AhR ligands are mainly consisted of tryptophan (Trp) metabolites; dietary Trp restriction, blocking the key Trp metabolism rate-limiting enzyme IDO1 or inhibition of cellular Trp importation also show similar effect as AhR inhibition. Clinically, BC patients with higher intratumoral expression of AhR or stronger intratumoral Trp metabolism (higher IDO1 or Kyn levels) that lead to higher AhR activation show worse response rate to neoadjuvant chemotherapy (NAC).