title: Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth.
abstract: Increasing evidence showed that Toll-like receptors (TLR), key receptors in innate immunity, play a role in cancer progression and development but activation of different TLRs might exhibit the exact opposite outcome, antitumor or protumor effects. TLR function has been extensively studied in innate immune cells, so we investigated the role of TLR signaling in breast cancer epithelial cells. We found that TLR5 was highly expressed in breast carcinomas and that TLR5 signaling pathway is overly responsive in breast cancer cells. Interestingly, flagellin/TLR5 signaling in breast cancer cells inhibits cell proliferation and an anchorage-independent growth, a hallmark of tumorigenic transformation. In addition, the secretion of soluble factors induced by flagellin contributed to the growth-inhibitory activity in an autocrine fashion. The inhibitory activity was further confirmed in mouse xenografts of human breast cancer cells. These findings indicate that TLR5 activation by flagellin mediates innate immune response to elicit potent antitumor activity in breast cancer cells themselves, which may serve as a novel therapeutic target for human breast cancer therapy.
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Cai
authors.forename: Amir
authors.initials: A
authors.lastname: Sanchez
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Shi
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Dekai
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D005408:Flagellin / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051198:Toll-Like Receptor 5 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin