| Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation |
| Xu, C; Wang, YF; Tu, Q; Zhang, ZY; Chen, MR; Mwangi, J; Li, YX; Jin, Y; Zhao, XD; Lai, R
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| 2019
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| 发表期刊 | ONCOGENE
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| ISSN | 0950-9232
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| 卷号 | 38期号:11页码:1832-1844 |
| 摘要 | Pancreatic cancer remains one of the deadliest human cancers despite current advances in conventional therapeutics including surgery and adjuvant therapies. Here, we showed that LZ1, a peptide derived from a snake venom cathelicidin, significantly inhibited growth of pancreatic cancer cells by inducing autophagy-dependent cell death both in vitro and in vivo. The LZ1-induced cell death was blocked by pharmacological or genetic inhibition of autophagy. In orthotopic model of pancreatic cancer, systemic administration of LZ1 (1-4 mg/kg) exhibited remarkable antitumor efficacy, significantly prolonged mice survival, and showed negligible adverse effects by comparison with gemcitabine (20 mg/kg). Mechanistic studies revealed that LZ1 acts through binding to nucleolin, whose expression on cell surface is frequently increased in pancreatic cancer cells. LZ1 binding triggers degradation of surface-expressed nucleolin. This leads to activation of 5'-AMP kinase which results in suppression of mTORC1 activity and induction of autophagic flux. These data suggest that LZ1, targeting nucleolin-AMPK-autophagy axis, is a promising lead for the development of therapeutic agents against pancreatic cancer. |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13214
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| 专题 | 科研部门_天然药物功能蛋白质学科组（赖仞）
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推荐引用方式
GB/T 7714 |
Xu, C,Wang, YF,Tu, Q,et al. Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation[J]. ONCOGENE,2019,38(11):1832-1844.
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| APA |
Xu, C.,Wang, YF.,Tu, Q.,Zhang, ZY.,Chen, MR.,...&Lai, R.(2019).Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation.ONCOGENE,38(11),1832-1844.
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| MLA |
Xu, C,et al."Targeting surface nucleolin induces autophagy-dependent cell death in pancreatic cancer via AMPK activation".ONCOGENE 38.11(2019):1832-1844.
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