硼替佐米通过 JNK 激活诱导头颈部鳞状细胞癌细胞自噬。
Bortezomib induces autophagy in head and neck squamous cell carcinoma cells via JNK activation.
机构信息
Department of Medicine, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
出版信息
Cancer Lett. 2012 Jan 1;314(1):102-7. doi: 10.1016/j.canlet.2011.09.020. Epub 2011 Sep 24.
Abstract
The molecular mechanism of autophagy induction following proteasome inhibition is not fully understood. We report that the proteasome inhibitor bortezomib potently induces autophagy in head and neck squamous cell carcinoma (HNSCC) cells, as demonstrated by autophagosome formation and induction of complete autophagic flux. Bortezomib treatment led to phosphorylation/activation of jun N-terminal kinase (JNK) enzymes and JNK-dependent phosphorylation of Bcl-2 on serine 70. Pharmacologic inhibition of JNK, but not p38 MAPK, dramatically inhibited bortezomib induction of autophagy regulatory proteins and autophagosome formation. These results demonstrate a key requirement for JNK signaling in the activation of autophagy by bortezomib.
摘要
蛋白酶体抑制后自噬诱导的分子机制尚不完全清楚。我们报告称，蛋白酶体抑制剂硼替佐米可强烈诱导头颈部鳞状细胞癌（HNSCC）细胞发生自噬，这可通过自噬体形成和完全自噬流的诱导来证明。硼替佐米处理导致 jun N 末端激酶（JNK）酶的磷酸化/激活，以及 Bcl-2 丝氨酸 70 上的 JNK 依赖性磷酸化。JNK 而不是 p38 MAPK 的药理学抑制显著抑制硼替佐米诱导的自噬调节蛋白和自噬体形成。这些结果表明 JNK 信号在硼替佐米激活自噬中起关键作用。
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