The pleipotent biological effects of tumor necrosis factor alpha,tumor necrosis factor receptor and multi-signal adaptor proteins in synergistic regulation in breast cancer
Xu Licheng
Fu Zhanpei
Wu Yeqin
Wang Gangping
Abstract：Breast cancer ranks first in the incidence rate of malignant tumors among women,posing a global public health issue.This article reviews the selective targeting effects of tumor necrosis factor alpha(TNF-α)and tumor necrosis factor receptor(TNFR)1 and TNFR2 in breast cancer and related therapeutic strategies,the expression and functions of TNFR1 and TNFR2 in different subtypes of breast cancer,as well as the dual biological effects and mechanisms of TNF-α induced apoptosis and anti-apoptosis.TNF-α and TNFR inhibit the phosphorylation of signal transducer and activator of transcription 5(STAT5)by interacting with multiple signal adaptor proteins,affect the function of breast cells,influence immune escape and drug resistance through the function of immune cells in the tumor microenvironment,resist TNF-α induced apoptosis,and induce tumor stemness and epithelial-mesenchymal transition of breast cancer.The complex signal transduction mechanism and the characteristic of playing different roles after binding to different receptors make TNF-α highly specific and complex in cellular signal transduction,suggesting that selective targeting of TNFR1 and TNFR2 may have more advantages than the traditional total TNF blocking therapy.
Keywords：Breast cancerTumor necrosis factor alphaTumor necrosis factor receptorNuclear factor-κBTumor microenvironmenCancer stemnessEpithelial-mesenchymal transitionSignal transduction
Publication Date：2025-04-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 127-133 )