肉豆蔻酰化的TMEM39AS41是一种可穿透细胞的肽，可导致肺癌细胞死亡。
Myristoylated TMEM39AS41, a cell-permeable peptide, causes lung cancer cell death.
作者信息
Park Sungjin, Kim Minhee, Hong Youngeun, Lee Hyunji, Tran Quangdon, Kim Chaeyeong, Kwon So Hee, Park Jisoo, Park Jongsun, Kim Seon-Hwan
机构信息
1Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015 Korea.
2Department of Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, 35015 Korea.
出版信息
Toxicol Res. 2020 Feb 7;36(2):123-130. doi: 10.1007/s43188-020-00038-1. eCollection 2020 Apr.
Abstract
Lung cancer is the most common cause of cancer-associated death worldwide. Most patients with non-small cell lung cancer die within several years of the initial diagnosis, and new therapies are desperately needed. Transmembrane protein (TMEM) 39AS41, a synthetic peptide, was generated from the protein kinase B substrate motif GLRNRNGSAIGLPVP found in the human TMEM39A protein. Myristic acid was conjugated to the N-terminus of the peptide to confer cell permeability. In this study, we found that in vitro TMEM39AS41 peptide led to cell death via inhibition of inflammation/autophagy pathways in KRAS-mutated cell and tissues. In addition, TMEM39A, at a dose of 30 mg/kg, significantly suppressed tumor growth in KRAS non-small cell lung cancer mice. These results suggest that the TMEM39AS41 peptide could have therapeutic potential for lung cancer.
摘要
肺癌是全球癌症相关死亡的最常见原因。大多数非小细胞肺癌患者在初次诊断后的几年内死亡，因此迫切需要新的治疗方法。跨膜蛋白（TMEM）39AS41是一种合成肽，由在人类TMEM39A蛋白中发现的蛋白激酶B底物基序GLRNRNGSAIGLPVP生成。肉豆蔻酸与该肽的N端缀合以赋予细胞通透性。在本研究中，我们发现体外TMEM39AS41肽通过抑制KRAS突变细胞和组织中的炎症/自噬途径导致细胞死亡。此外，TMEM39A以30mg/kg的剂量显著抑制KRAS非小细胞肺癌小鼠的肿瘤生长。这些结果表明，TMEM39AS41肽可能对肺癌具有治疗潜力。
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