Title:LPS/TLR4 Pathways in Breast Cancer: Insights into Cell Signalling
Volume: 29
Issue: 13
Author(s): Rizwana Afroz, E.M. Tanvir, Mousumi Tania, Junjiang Fu, Mohammad Amjad Kamal and Md. Asaduzzaman Khan*
Affiliation:
- Key Laboratory of Epigenetics and Oncology, The Research Center for Preclinical Medicine,
Southwest Medical University, Luzhou, Sichuan, China
Keywords:
Breast cancer, toll like receptor 4, lipopolysaccharide, signalling pathway, cancer therapy, 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.