PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer
PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer
复制标题
PI3K/Akt/mTOR 信号传导协调小细胞肺癌的表型转变和化疗耐药
DOI：
10.1016/j.jgg.2021.04.001
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发表时间：
2021-07-20
影响因子：
5.9
通讯作者：
Ji, Hongbin
中科院分区：
文献类型：
--
作者：
Li, Xuefeng;Li, Cheng;Ji, Hongbin
小细胞肺癌（SCLC）是一种表型异质性疾病，预后极差，主要原因是化疗耐药的迅速发展。然而，小细胞肺癌的生长表型和化疗耐药性之间的关系仍不清楚。通过综合生物信息学分析，我们发现SCLC表型的异质性与不同的化疗敏感性显著相关。贴壁或半贴壁SCLC细胞富含PI 3 K/Akt/mTOR途径的活化，并且具有高度的化学抗性。从机制上讲，PI 3 K/Akt/mTOR通路的激活促进了从悬浮生长模式到粘附生长模式的表型转变，并赋予SCLC细胞化学抗性。这种化学抗性可以通过将化学疗法与PI 3 K/Akt/mTOR通路抑制剂组合来在很大程度上克服。我们的研究结果支持PI 3 K/Akt/mTOR通路在SCLC表型转变和化疗耐药性中起重要作用，这对改善SCLC治疗具有重要的临床意义。中国科学院遗传与发育生物学研究所版权所有（C）2021由Elsevier Limited和Science Press出版。All rights reserved.
Small cell lung cancer (SCLC) is a phenotypically heterogeneous disease with an extremely poor prognosis, which is mainly attributed to the rapid development of resistance to chemotherapy. However, the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear. Through comprehensive bioinformatic analyses, we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy. Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant. Mechanistically, activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance. Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors. Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance, which holds important clinical implications for improving SCLC treatment. Copyright (C) 2021, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.