TLRs: Linking inflammation and breast cancer Khyati Bhatelia, Kritarth Singh, Rajesh Singh ⁎ Department of Bio-Chemistry, The M.S. University of Baroda, Vadodara 390002, Gujarat, India abstract article info Article history: Received 15 July 2014 Accepted 28 July 2014 Available online 3 August 2014 Keywords: TLRs NF-κB Inflammation Breast cancer Breast cancer is one of the leading causes of mortality in the females. Intensive efforts have been made to under- stand the molecular mechanisms of pathogenesis of breast cancer. The physiological conditions that lead to tu- morigenesis including breast cancer are not well understood. Toll like receptors (TLRs) are essential components of innate immune system that protect the host against bacterial and viral infection. The emerging evidences suggest that TLRs are activated through pathogen associated molecular patterns (PAMPs) as well as endogenous molecules, which lead to the activation of inflammatory pathways. This leads to increased levels of several pro-inflammatory cytokines and chemokines mounting inflammation. Several evidences support the view that chronic inflammation can lead to cancerous condition. Inflammation aids in tumor progression and metastasis. Association of inflammation with breast cancer is emerging. TLR mediated activation of NF-κB and IRF is an essential link connecting inflammation to cancer. The recent reports provide several evidences, which suggest the important role of TLRs in breast cancer pathogenesis and recurrence. The current review focuses on emerging studies suggesting the strong linkages of TLR mediated regulation of inflammation during breast cancer and its metastasis emphasizing the initiation of the systematic study. © 2014 Elsevier Inc. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2350 1.1. TLRs: link between inflammation and cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2351 1.2. TLR and breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2352 1.3. TLR: the lessons from breast cell lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2352 1.4. TLR implication in breast cancer metastasis: the patient studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2353 1.5. TLR and NF-κB: linking inflammation and breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2354 1.6. TLR: implication in therapeutics of breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2355 1.7. Type-I IFNs: emerging therapeutic for breast cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2356 2. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2356 Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2356 Acknowledgment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2356 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2356 1. Introduction Breast cancer is the second most common cancer diagnosed world- wide. More than 1.3 million women worldwide are diagnosed with breast cancer each year [1]. Breast cancer rate has increased by 0.4% per year from 1975 to 1990; however its death rate decreased thereafter by 2.2% from 1990 to 2007 [2]. In spite of decrease in breast cancer incidence, about half-a-million women still die because of breast cancer each year [1,3]. The high figures of incidences and mortality, even with the advancement of primary screening and diagnosis, suggest the need to systematically investigate the cause and pathogenesis of breast cancer. The physiological conditions that stimulate proliferation and growth of somatic cells leading to neoplasia and carcinoma are not well under- stood. The relationship between inflammation and cancer is emerging. The inflammatory diseases increase the risk of developing cancer [2, 4–7]. For example, patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer [8]. Similarly, Cellular Signalling 26 (2014) 2350–2357 ⁎ Corresponding author at: Department of Bio-Chemistry, Faculty of Science, The M.S. University of Baroda, Vadodara 390002, Gujarat, India. Tel.: +91 265 2759594. E-mail address: singhraj1975@gmail.com (R. Singh). http://dx.doi.org/10.1016/j.cellsig.2014.07.035 0898-6568/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Cellular Signalling journal homepage: www.elsevier.com/locate/cellsig