PI3K/AKT/mTOR通路
蛋白激酶B
乙酰胆碱
甲状腺癌
癌细胞
癌症研究
免疫系统
癌症干细胞
癌症
细胞生物学
生物
内科学
化学
内分泌学
信号转导
干细胞
甲状腺
免疫学
医学
作者
Zhenglin Wang,Wei Liu,Cong Wang,Yinan Li,Zhilong Ai
标识
DOI:10.1016/j.canlet.2019.12.009
摘要
Nerves infiltrate the tumor microenvironment and stimulate the growth of cancer cells through the secretion of neurotransmitters. However, the contributions of nerves to the self-renewal capacity of cancer stem cells (CSCs) remain largely unknown. In this study, we found that CD133+ cancer cells were responsible for the initiation of thyroid cancer. Neurons were juxtaposed with CD133+ cells in thyroid cancer tissues. Acetylcholine, one of the most abundant neurotransmitters, promoted CD133 Y828 phosphorylation, and subsequently increased the interaction between CD133 and PI3K regulatory subunit p85, resulting in the activation of the PI3K-Akt pathway. Acetylcholine increased the self-renewal ability of CD133+ thyroid cancer cells through activation of CD133-Akt pathway. Furthermore, acetylcholine promoted the expression of the immune regulator PD-L1 through the activation of the CD133-Akt pathway, resulting in the resistance of CD133+ thyroid cancer cells to CD8+ T cells. However, acetylcholine receptor antagonist 4-DAMP blocked the positive effects of acetylcholine on the self-renewal and immune escape of CD133+ thyroid cancer cells. Taken together, these data suggest that acetylcholine increases the self-renewal and immune escape abilities of CD133+ thyroid cancer cells through the activation of the CD133-Akt pathway.
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