J Cancer 2021; 12(23):6979-6988. doi:10.7150/jca.60974 This issue

Research Paper

Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade

Yihuan Pu1, Mingxing Lei2,3, Yangmei Chen1, Yanran Huang4, Lingzhao Zhang1, Jiayi Chen1, Yujie Zhang1, Xinyi Shao1, Lin Liu1, Jin Chen1✉

1. Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
2. 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China.
3. Key Laboratory of Biorheological Science and Technology of the Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
4. Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Pu Y, Lei M, Chen Y, Huang Y, Zhang L, Chen J, Zhang Y, Shao X, Liu L, Chen J. Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade. J Cancer 2021; 12(23):6979-6988. doi:10.7150/jca.60974. Available from https://www.jcancer.org/v12p6979.htm

File import instruction

Abstract

Graphic abstract

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.

Keywords: Melanoma, Hey1, GRB2/PI3K/AKT signaling, EMT, Invasion