LPS/TLR4 Pathways in Breast Cancer: Insights into Cell Signalling

Abstract

Background: Cancer cells are usually recognized as foreign particles by the immune cells. Mounting evidence suggest an important link between toll-like receptors (TLRs) and carcinogenesis. This review article focused on the role of TLRs, especially TLR4, in breast cancer.

Methods: Research data on TLRs and cancer was explored in PubMed, Scopus, Google Scholar and reviewed. Although some pioneer works are referenced, papers published in the last ten years were mostly cited.

Results: TLRs are widely investigated pattern recognition receptors (PRR), and TLR4 is the most studied TLRs, implicated with the occurrence of several types of cancers, including breast cancer. TLR4 activation occurs via the binding of its ligand lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria. Upon LPS binding, TLR4 dimerizes and recruits downstream signalling and/or adapter molecules, leading to gene expression related to cancer cell proliferation, survival, invasion, and metastasis. Although LPS/TLR4 signalling seems a single signal transduction pathway, the TLR4 activation results in the activation of multiple diverse intracellular networks with huge cellular responses in both immune and cancer cells. The role of TLR4 in the growth, invasion, and metastasis of breast cancer is attracting huge attention in oncology research. Several clinical and preclinical studies utilize both TLR4 agonists and antagonists as a treatment option for cancer therapy, either as monotherapy or adjuvants for vaccine development.

Conclusion: This review narrates the role of LPS/TLR4 signalling in breast cancer development and future prospects for targeting LPS/TLR4 axis in the treatment of breast cancer.

Keywords: Breast cancer; cancer therapy; cell signalling; lipopolysaccharide; signalling pathway; toll like receptor 4.