EGFR tyrosine kinase inhibitors differentially affect autophagy in head and neck squamous cell carcinoma
EGFR tyrosine kinase inhibitors differentially affect autophagy in head and neck squamous cell carcinoma
复制标题
EGFR 酪氨酸激酶抑制剂对头颈鳞状细胞癌自噬的影响不同
DOI：
10.1016/j.bbrc.2017.03.157
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发表时间：
2017-05-13
影响因子：
3.1
通讯作者：
Sun, Yue
中科院分区：
文献类型：
--
作者：
Cai, Jinyang;Sun, Ming;Sun, Yue
头颈部鳞状细胞癌(HNSCC)是全球第六大最常见的癌症。大多数HNSCC过度表达表皮生长因子受体(EGFR)，这是一种促进HNSCC生长和转移的重要受体酪氨酸激酶(RTK)。因此，EGFR已成为治疗HNSCC的重要靶点。抑制EGFR可刺激癌细胞的自噬。然而，自噬在EGFR抑制剂诱导的肿瘤抑制中的作用仍存在争议。在这里，我们揭示了第一代和第二代EGFR酪氨酸激酶抑制剂(TKI)对HNSCC自噬的不同影响。第二代EGFR TKI对自噬的影响比第一代TKI强得多。第二代EGFR TKI不仅促进自噬起始信号，而且通过干扰溶酶体功能来阻断自噬通量，表明了EGFR TKI调控癌细胞自噬的新机制。阻断自噬的启动并不影响第二代EGFR TKIs诱导的HNSCC生长抑制。这表明第二代EGFR TKI对HNSCC的抗生长作用不依赖于自噬。(C)2017 Elsevier Inc.保留所有权利。
Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide. The majority of HNSCCs overexpress Epidermal Growth Factor Receptor (EGFR), an essential receptor tyrosine kinase (RTK) that promotes HNSCC growth and metastasis. Therefore, EGFR has been used as an important therapeutic target to treat HNSCC. Inhibition of EGFR stimulates autophagy in cancer cells. However, the role of autophagy in EGFR inhibitor-induced cancer suppression is still in a debate. Here, we reveal that the first-and the second-generation EGFR tyrosine kinase inhibitors (TKIs) differentially affect HNSCC autophagy. The second-generation EGFR TKIs have much stronger effects on autophagy than the first-generation TKIs. The second-generation EGFR TKIs not only promote autophagy initiation signaling but also block autophagic flux by disturbing the lysosomes function, indicating a novel mechanism by which EGFR TKIs modulate cancer cell autophagy. Blocking the initiation of autophagy does not affect the second-generation EGFR TKIs-induced HNSCC growth suppression. This suggests that the anti-growth effect of the second-generation EGFR TKIs on HNSCC is not dependent on autophagy. (C) 2017 Elsevier Inc. All rights reserved.