文献类型：期刊文献

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

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

第一作者：Yang, Hange

通信作者：Zhang, HL[1];Mou, LY[1];Wang, R[1];Wang, R[2];Mou, LY[3]

机构：[1]Lanzhou Univ, Chinese Acad Med Sci, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 2019RU066, Lanzhou, Gansu, Peoples R China; Lanzhou Univ, Chinese Acad Med Sci, Res Unit Peptide Sci, 2019RU066, Lanzhou, Gansu, Peoples R China;[2]Inst Mat Med, Chinese Acad Med Sci, Beijing, Peoples R China;[3]Gansu Univ Chinese Med, Gansu Univ, Key Lab Mol Med & Chinese Med Prevent & Treatment, Coll Pharm, Lanzhou, Peoples R China;[4]Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Peoples R China

第一机构：Lanzhou Univ, Chinese Acad Med Sci, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 2019RU066, Lanzhou, Gansu, Peoples R China,Lanzhou Univ, Chinese Acad Med Sci, Res Unit Peptide Sci, 2019RU066, Lanzhou, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Chinese Acad Med Sci, Sch Basic Med Sci, Key Lab Preclin Study New Drugs Gansu Prov, 2019RU066, Lanzhou, Gansu, Peoples R China;[2]corresponding author), Inst Mat Med, Chinese Acad Med Sci, Beijing, Peoples R China;[3]corresponding author), Lanzhou Univ, Sch Life Sci, Lanzhou 730000, Peoples R China.

年份：2023

卷号：8

期号：1

外文期刊名：SIGNAL TRANSDUCTION AND TARGETED THERAPY

收录：;Scopus(收录号：2-s2.0-85176399949);WOS:【SCI-EXPANDED(收录号:WOS:001101199400001)】；

基金：We sincerely thank Dr Shuchang Lai and Prof Chu Wang (Peking University) for their assistance with the LC-MS/MS analysis. This study was 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), and the Fundamental Research Funds for the Central Universities (No. lzujbky-2023-11, lzujbky-2023-ct02, lzujbky-2023-it19, China).

语种：英文

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 (PITP alpha/beta) 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 PITP alpha/beta expression is closely correlated with the poor prognosis. Target identification by chemical proteomic methods revealed that microcolin H, a naturally occurring marine lipopeptide, directly binds PITP alpha/beta and 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 PITP alpha/beta, microcolin H induced autophagic cell death in tumours with efficient anti-proliferating activity, which sheds light on PITP alpha/beta as a promising therapeutic target for cancer treatment.