文献类型：期刊文献

中文题名：Microcolin H, a novel autophagy inducer, exerts potent antitumour activity by targeting PITPα/β

作者：Hange Yang[1];Xiaowei Zhang[1];Cong Wang[1];Hailong Zhang[1];Juan Yi[1];Kun Wang[2];Yanzhe Hou[1];Peihong Ji[1];Xiaojie Jin[3];Chenghao Li[3];Min Zhang[3];Shan Huang[1];Haoyuan Jia[1,4];Kuan Hu[2];Lingyun Mou[1,4];Rui Wang[1,2]

第一作者：Hange Yang

机构：[1]Key Laboratory of Preclinical Study for New Drugs of Gansu Province,School of Basic Medical Sciences&Research Unit of Peptide Science,Chinese Academy of Medical Sciences,2019RU066,Lanzhou University,Lanzhou,Gansu,P.R.China;[2]Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing,P.R.China;[3]Gansu University Key Laboratory for Molecular Medicine&Chinese Medicine Prevention and Treatment of Major Diseases,College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou,China;[4]School of Life Science,Lanzhou University,730000 Lanzhou,P.R.China

第一机构：Key Laboratory of Preclinical Study for New Drugs of Gansu Province,School of Basic Medical Sciences&Research Unit of Peptide Science,Chinese Academy of Medical Sciences,2019RU066,Lanzhou University,Lanzhou,Gansu,P.R.China

年份：2023

卷号：8

期号：12

起止页码：5931

中文期刊名：Signal Transduction and Targeted Therapy

外文期刊名：信号转导与靶向治疗（英文）

收录：CSTPCD;;Scopus;CSCD:【CSCD2023_2024】；PubMed;

基金：supported by the Program for the Ministry of Education“Peptide Drugs”Innovation Team(No.IRT_15R27,China);the National Natural Science Foundation of China(21807053);the CAMS Innovation Fund for Medical Sciences(CIFMS,Nos.2019-I2M-5-074,2021-I2M-1-026,2021-I2M-3-001,2022-I2M-2-002,China);the Fundamental Research Funds for the Central Universities(No.lzujbky-2023-11,lzujbky-2023-ct02,lzujbky-2023-it19,China).

语种：英文

中文关键词：tumour;metabolism;nude;

摘要：The identification of effective drug targets and the development of bioactive molecules are areas of high need in cancer therapy.The phosphatidylinositol transfer protein alpha/beta isoform(PITPα/β)has been reported to play an essential role in integrating phosphoinositide trafficking and lipid metabolism in diverse cellular processes but remains unexplored as a potential target for cancer treatment.Herein,data analysis of clinical cancer samples revealed that PITPα/βexpression is closely correlated with the poor prognosis.Target identification by chemical proteomic methods revealed that microcolin H,a naturally occurring marine lipopeptide,directly binds PITPα/βand displays antiproliferative activity on different types of tumour cell lines.Furthermore,we identified that microcolin H treatment increased the conversion of LC3I to LC3II,accompanied by a reduction of the level of p62 in cancer cells,leading to autophagic cell death.Moreover,microcolin H showed preeminent antitumour efficacy in nude mouse subcutaneous tumour models with low toxicity.Our discoveries revealed that by targeting PITPα/β,microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity,which sheds light on PITPα/βas a promising therapeutic target for cancer treatment.