Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade.
Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade.
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DOI：
10.7150/jca.60974
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发表时间：
2021
影响因子：
3.9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Pu Y;Lei M;Chen Y;Huang Y;Zhang L;Chen J;Zhang Y;Shao X;Liu L;Chen J
越来越多的证据表明，Notch信号调节恶性黑色素瘤的多种细胞内生物学过程。然而，Notch信号如何被转导来影响黑色素瘤细胞的行为在很大程度上仍然难以捉摸。在这里，我们发现Notch信号下游靶Hey1通过Grb2/PI3K/AKT途径促进黑色素瘤细胞的迁移和侵袭。首先，生物信息学工具、免疫组织化学和Western blotting分析表明Hey1在黑色素瘤中的表达增加。然后，体内和体外实验都表明，Hey1促进了黑色素瘤细胞的恶性行为。高通量RNA测序分析表明，抑制Hey1导致黑色素瘤细胞Grb2表达降低。功能实验证实Hey1正向调节Grb2/PI3K/AKT通路，影响黑色素瘤细胞的迁移和侵袭。综上所述，我们的结果提示Hey1通过调节Grb2/PI3K/AKT通路促进黑色素瘤细胞的侵袭和转移。我们的研究为肿瘤生物学提供了潜在的治疗方法。
Increasing evidence indicates that Notch signaling regulates multiple intracellular biological processes in malignant melanoma. Whereas how Notch signaling is transduced to influence melanoma cell behaviors remains largely elusive. Here we show that the Notch signaling downstream target Hey1 promotes migration and invasion of melanoma cells via the GRB2/PI3K/AKT pathway. First, bioinformatics tools, immunohistochemistry, and Western blotting analysis showed that the expression of Hey1 is increased in melanoma. Then, both in vivo and in vitro experiments showed that Hey1 promotes the malignant behaviour of the melanoma cells. High-throughput RNA-sequencing analysis revealed that inhibition of Hey1 results in decreased GRB2 expression in melanoma cells. Last, functional experiments confirmed that Hey1 positively regulates GRB2/PI3K/AKT pathway to influence migration and invasion of melanoma cells. In summary, our results suggest that Hey1 promotes the invasion and metastasis of melanoma cells by regulating GRB2/PI3K/AKT pathway. Our study provides potential therapeutics in tumor biology.