AXL upregulates c‑Myc expression through AKT and ERK signaling pathways in breast cancers

Xiaobai Sun; Hong Chen; Shuling You; Zhikang Tian; Zhaoyu Wang; Fulin Liu; Wenyi Hu; Hao Zhang; Guoan Zhang; Hongli Zhao; Qingwei Guo

doi:10.3892/mco.2023.2618

AXL upregulates c‑Myc expression through AKT and ERK signaling pathways in breast cancers

Mol Clin Oncol. 2023 Feb 8;18(3):22. doi: 10.3892/mco.2023.2618. eCollection 2023 Mar.

Authors

Xiaobai Sun¹, Hong Chen², Shuling You¹, Zhikang Tian³, Zhaoyu Wang³, Fulin Liu³, Wenyi Hu³, Hao Zhang³, Guoan Zhang⁴, Hongli Zhao⁵, Qingwei Guo⁶

Affiliations

¹ Department of Pathology, Jinan Adicon Clinical Laboratory, Jinan, Shandong 250000, P.R. China.
² Clinical Laboratory, The Third People's Hospital of Jinan, Jinan, Shandong 250132, P.R. China.
³ College of Basic Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China.
⁴ Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Forensic Science Center of Jining Medical University, Jining, Shandong 272067, P.R. China.
⁵ Department of Digestive System, Shandong Institute of Parasitic Diseases, Shandong First Medical University and Shandong Academy of Medical Sciences, Jining, Shandong 272067, P.R. China.
⁶ Department of Hematology, Jinan Children's Hospital, Jinan, Shandong 250132, P.R. China.

Abstract

Breast cancer (BC) is common worldwide. c-Myc and AXL are both overexpressed in BC, promoting its progression. The present study aimed to investigate the role of AXL in c-Myc expression in BC. Overexpression of AXL increased c-Myc expression while knockdown of AXL decreased c-Myc expression as determined by western blot analysis. Pharmaceutical inhibition of AXL also suppressed c-Myc expression. AKT and ERK inhibitor LY294002 and U0126 suppressed c-Myc expression, respectively. AXL overexpression which activates AKT and ERK signaling, upregulates c-Myc expression, while kinase-dead AXL which cannot activate AKT and ERK signaling, does not upregulate c-Myc expression, emphasizing the important role of these two signaling pathways in c-Myc upregulation. Finally, expression data of BC tissues from The Cancer Proteome Atlas displayed an association between AXL and c-Myc. Taken together, the present study revealed that AXL upregulates c-Myc expression through AKT and ERK signaling pathways in BC.

Keywords: AXL; breast cancer; c-Myc.

Grants and funding

Funding: The present study was supported by innovation and entrepreneurship training program for college students of Jining Medical University (grant no. cx2021138), the Enterprise Technology Innovation Project of Jinan (grant no. 201940901085) and the Project of Medicine and Health Development Plan of Shandong (grant no. 2019WS176).