EGFR Promotes the Development of Triple Negative Breast Cancer Through JAK/STAT3 Signaling

Xiang Song,1 Zhaoyun Liu,1,2 Zhiyong Yu1 1Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, People’s Republic of China; 2School of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Zhiyong YuDepartment of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan 250117, Shandong, People’s Republic of ChinaEmail drzhiyongyu@aliyun.comPurpose: To investigate the role of EGFR and STAT3 in breast cancer development and progression.Methods: Through bioinformatics analysis differently expressed genes (DEGs) including EGFR and STAT3 were identified in breast cancer tissue. QRT-PCR and Western blot analysis were used to investigate EGFR and STAT3 levels in breast cancer tissues and cells. The influence of EGFR and STAT3 on the breast cancer cell proliferation (CCK-8 assay, clone formation assays), migration (wound healing assays) and invasion (transwell assays) were investigated. The influence of EGFR on breast cancer in vivo was examined by Nude mouse transplantation tumor experiments and immunohistochemistry (IHC) staining. The effects of EGFR on breast cancer signaling were assessed via Western blot.Results: Both EGFR and p-STAT3 were up-regulated in breast cancer tissues and cell lines. EGFR expression was positively associated with p-STAT3. Moreover, EGFR and p-STAT3 activity enhanced the proliferation and invasion of tumor cells. Breast cancer cell growth was dramatically inhibited by EGFR silencing in vivo.Conclusion: EGFR promotes breast cancer progression via STAT3 phosphorylation and JAK/STAT3 signaling.Keywords: EGFR, STAT3, p-STAT3, breast cancer