MAP1S controls breast cancer cell TLR5 signaling pathway and promotes TLR5 signaling-based tumor suppression.
Targeting TLR5 signaling in breast cancer represents a novel strategy in cancer immunotherapy. However, the underlying mechanism by which TLR5 signaling inhibits cancer cell proliferation and tumor growth has not been elucidated. In this study, we found TLR5 agonist flagellin inhibited the cell state of activation and induced autophagy, and reported that autophagy protein MAP1S regulated the flagellin/TLR5 signaling pathway in breast cancer cells through enhancement of NF-κB activity and cytokine secretion. Remarkably, MAP1S played a critical role in tumor suppression induced by flagellin, and knockdown of MAP1S almost completely abrogated the suppression of tumor growth and migration by flagellin treatment. In addition, elevated expression of MAP1S in response to flagellin feed-back regulated tumor inflammatory microenvironment in the late stages of TLR5 signaling through degradation of MyD88 in autophagy process. These results indicate a mechanism of antitumor activity that involves MAP1S-controlled TLR5 signaling in breast cancer.
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Ming
M
Shi
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Yuanfei
Y
Yao
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Fang
F
Han
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Yiqun
Y
Li
School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
Yu
Y
Li
D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C493240:MAP1S protein, human; C507779:MYD88 protein, human; D008869:Microtubule-Associated Proteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin