Details

Autor(en) / Beteiligte

• Yu, Jiao-jiao
• Zhou, Dan-dan
• Yang, Xiao-xiao
• Cui, Bing
• Tan, Feng-wei
• Wang, Junjian
• Li, Ke
• Shang, Shuang
• Zhang, Cheng
• Lv, Xiao-xi
• Zhang, Xiao-wei
• Liu, Shan-shan
• Yu, Jin-mei
• Wang, Feng
• Huang, Bo
• Hua, Fang
• Hu, Zhuo-Wei

Titel

TRIB3-EGFR interaction promotes lung cancer progression and defines a therapeutic target

Ist Teil von

• Nature communications, 2020-07, Vol.11 (1), p.1-16, Article 3660

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.