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胰岛素样生长因子1受体（IGF1R）通过信号转导与转录激活因子3（STAT3）/蛋白激酶B（AKT）轴促进神经母细胞瘤中的上皮-间质转化和癌症干细胞特性。

IGF1R facilitates epithelial-mesenchymal transition and cancer stem cell properties in neuroblastoma via the STAT3/AKT axis.

作者信息

Wang Xiao-Hui, Wu Hai-Ying, Gao Jian, Wang Xu-Hui, Gao Tian-Hui, Zhang Shu-Feng

机构信息

Department of Pediatric Surgery, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, People's Republic of China.

Department of Obstetrics, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou 450003, People's Republic of China.

出版信息

Cancer Manag Res. 2019 Jun 12;11:5459-5472. doi: 10.2147/CMAR.S196862. eCollection 2019.

DOI:10.2147/CMAR.S196862
PMID:31354352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6580139/
Abstract

BACKGROUND

Neuroblastoma (NB) displays the most heterogeneity in clinical manifestation. The insulin-like growth factor 1 receptor (IGF1R) has long been recognized for its role in tumourigenesis and growth. The IGF/IGF1R pathway is important in maintaining cell survival. It is reported that IGF1R participates in the occurrence of NB, but the mechanism is still unclear.

METHODS

Human NB cell lines IMR-32 and SH-SY5Y were recruited in this study. IGF1R was knocked down by transfection with short hairpin RNA. Signal transducer and activator of transcription 3 (STAT3) expression was inhibited by Cryptotanshinone treatment. Cell proliferation, migration, and invasion were determined by MTT assay, wound healing assay, and cell invasion assay, respectively. The cancer stem cell properties were characterized by tumour sphere formation assay and colony formation assay. The mRNA and protein expression levels of related proteins were detected by RT-PCR and Western blot, respectively.

RESULTS

The knockdown of IGF1R inhibits NB cell tumourigenesis and the epithelial-mesenchymal transition (EMT) of NB cells. Additionally, IGF1R was found to stimulate cancer stem cell-like properties in NPC cells. The knockdown of IGF1R significantly reduced the phosphorylation of AKT, and STAT3, indicating that the activation of the AKT and STAT3 pathways was inhibited by IGF1R knockdown. Furthermore, IGF1R was demonstrated to stimulate cancer stem cell-like properties in NB cells via the regulation of the STAT3/AKT axis.

CONCLUSION

IGF1R promotes cancer stem cell properties to facilitate EMT in neuroblastoma via the STAT3/AKT axis.

摘要

背景

神经母细胞瘤（NB）在临床表现上具有最大的异质性。胰岛素样生长因子1受体（IGF1R）长期以来因其在肿瘤发生和生长中的作用而被认可。IGF/IGF1R通路在维持细胞存活中很重要。据报道，IGF1R参与NB的发生，但其机制仍不清楚。

方法

本研究纳入了人NB细胞系IMR-32和SH-SY5Y。通过短发夹RNA转染敲低IGF1R。隐丹参酮处理抑制信号转导和转录激活因子3（STAT3）表达。分别通过MTT法、伤口愈合试验和细胞侵袭试验测定细胞增殖、迁移和侵袭。通过肿瘤球形成试验和集落形成试验表征癌症干细胞特性。分别通过RT-PCR和蛋白质印迹检测相关蛋白的mRNA和蛋白质表达水平。

结果

IGF1R的敲低抑制了NB细胞的肿瘤发生和NB细胞的上皮-间质转化（EMT）。此外，发现IGF1R刺激NPC细胞中癌症干细胞样特性。IGF1R的敲低显著降低了AKT和STAT3的磷酸化，表明IGF1R敲低抑制了AKT和STAT3通路的激活。此外，证明IGF1R通过调节STAT3/AKT轴刺激NB细胞中的癌症干细胞样特性。

结论

IGF1R通过STAT3/AKT轴促进癌症干细胞特性，以促进神经母细胞瘤中的EMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/8500f4f6aab7/CMAR-11-5459-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/1a8045ea17e7/CMAR-11-5459-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/d16b78216240/CMAR-11-5459-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/ecb41ab39a1a/CMAR-11-5459-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/a3f358e8371c/CMAR-11-5459-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/8500f4f6aab7/CMAR-11-5459-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/1a8045ea17e7/CMAR-11-5459-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/d16b78216240/CMAR-11-5459-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/f8865aafb021/CMAR-11-5459-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/36d8c48df771/CMAR-11-5459-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/ecb41ab39a1a/CMAR-11-5459-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/a3f358e8371c/CMAR-11-5459-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e6/6580139/8500f4f6aab7/CMAR-11-5459-g0007.jpg

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