Proteolytic Release of the p75NTR Intracellular Domain by ADAM10 Promotes Metastasis and Resistance to Anoikis.
作者： Xin Bao , Jianbo Shi , Furong Xie , Zengying Liu , Jingshuang Yu
DOI: 10.1158/0008-5472.CAN-17-2789
关键词:
摘要: Resistance to anoikis allows cancer cells survive during systemic circulation; however, the mechanism underlying resistance remains unclear. Here we show that A disintegrin and metalloprotease 10 (ADAM10)-mediated cleavage of p75 neurotrophin receptor (p75NTR) subsequent generation p75NTR intracellular domain (ICD) endow with anoikis. ICD promoted expression TNF receptor-associated factor 6 (TRAF6), a critical intermediary in ICD-mediated signal transduction, at translational level. Cell detachment-induced activation EGFR triggered autoubiquitination TRAF6 by facilitating its dimerization, subsequently activated NFκB, eventually led resistance. ADAM10 also tumor metastasis formation vivo Together, our findings uncover previously unknown function for ADAM10-p75NTR ICD-TRAF6-NFκB axis preventing suggest as potential therapeutic targets.Significance: These identify signaling candidate therapy. Cancer Res; 78(9); 2262-76. ©2018 AACR.
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