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论文题目: Targeting Surface Nucleolin Induces Autophagy-dependent Cell Ceath in Pancreatic Cancer via AMPK Activation
作者: Xu C, Wang Y, Tu Q, Zhang Z, Chen M, Mwangi J, Li Y, Jin Y, Zhao X, Lai R
联系作者: rlai@mail.kiz.ac.cn
发表年度: 2018
DOI: doi: 10.1038/s41388-018-0556-x
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 pancreaticcancer 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, targetingnucleolin-AMPK-autophagy axis, is a promising lead for the development of therapeutic agents against pancreatic cancer

刊物名称: Oncogene
论文出处: https://www.nature.com/articles/s41388-018-0556-x
影响因子: 6.854(2016年)