MEGF11 is related to tumour recurrence in triple negative breast cancer via chemokine upregulation.

Autor: Chiu JH; Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. chiujh@ym.edu.tw.; Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC. chiujh@ym.edu.tw.; Department of Surgery, Cheng-Hsin General Hospital, Taipei, Taiwan, ROC. chiujh@ym.edu.tw., Tseng LM; Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.; Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC., Huang TT; Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.; Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA., Liu CY; Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.; Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC., Wang JY; Department of Orthopedics, Taipei-Veterans General Hospital, Taipei, Taiwan, ROC., Huang CP; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC., Tsai YF; Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC., Hsu CY; Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.; School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 May 15; Vol. 10 (1), pp. 8060. Date of Electronic Publication: 2020 May 15.
DOI: 10.1038/s41598-020-64950-0
Abstrakt: Our previous study demonstrated that upregulation of multiple epidermal growth factor-like domains 11 (MEGF11) gene expression is involved in the mechanism by which recurrence of Triple Negative Breast Cancer (TNBC) occurs. Our aim was to elucidate the role of MEGF11 expression in TNBC cells, both in vitro and in vivo, and in human tissue. Following MEGF11 gene knockdown (∆MEGF11) or over-expression in MDA-MB-231 and MB-468 cells, cell growth and chemokine gene expression were evaluated. In vivo, tumour growth of implanted human TNBC cells and the number of circulating 4T1 mouse tumour cells were measured. There was a significant decrease in cell growth via inhibition of AKT, NF-kB, CREB and AP-1 activation in ∆MEGF11 MDA-MB-231 and 468 cells. This also resulted, in vivo, in a suppression of tumour growth and a decrease in the number of mouse circulating 4T1 breast cancer cells. Surprisingly, overexpression of MEGF11 upregulated the expression of various chemokines and proinflammatory cytokines via AKT activation, but there was no increase in cell proliferation. MEGF11 was found to cross-talk positively with IL-17A signalling. Patients with tumours that over-expressed MEGF11 had a poorer prognosis. We conclude that MEGF11 plays an important role in tumour survival and that overexpression of MEGF11 induces both a cytokine and a chemokine cascade, which will favour the tumour microenvironment in terms of distant metastasis. MEGF11 might be a potential therapeutic target for preventing TNBC recurrence.
Databáze: MEDLINE
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