Pu Yihuan, Lei Mingxing, Chen Yangmei, Huang Yanran, Zhang Lingzhao, Chen Jiayi, Zhang Yujie, Shao Xinyi, Liu Lin, Chen Jin
Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China.
J Cancer. 2021 Oct 11;12(23):6979-6988. doi: 10.7150/jca.60974. eCollection 2021.
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 and 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.
越来越多的证据表明，Notch信号通路调节恶性黑色素瘤中的多种细胞内生物学过程。然而，Notch信号如何转导以影响黑色素瘤细胞行为在很大程度上仍然不清楚。在这里，我们表明Notch信号下游靶点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、免疫组织化学和蛋白质印迹分析表明，Hey1在黑色素瘤中的表达增加。然后，体内和体外实验均表明Hey1促进黑色素瘤细胞的恶性行为。高通量RNA测序分析显示，抑制Hey1会导致黑色素瘤细胞中GRB2表达降低。最后，功能实验证实Hey1正向调节GRB2/PI3K/AKT途径，以影响黑色素瘤细胞的迁移和侵袭。总之，我们的结果表明，Hey1通过调节GRB2/PI3K/AKT途径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。
