title: LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells.
abstract: Colorectal cancer (CRC) is the most commonly diagnosed cancer worldwide, and over 50% of patients will develop hepatic metastasis during the course of their disease. CXCR4 and its ligand, stromal cell-derived factor 1α (SDF-1α)/chemokine (C-X-C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we have shown that lipopolysaccharides (LPS) promoted the migratory capacity of colon cancer cells in vivo and in vitro, which correlated with the activation of SDF-1α/CXCR4 axis and epithelial-mesenchymal transition (EMT) occurrence. Additionally, we found that LPS-induced CXCR4 expression and EMT through NF-κB signaling pathway activation. And inhibition of NF-κB pathway, which recovered the epithelial phenotype and attenuated CXCR4 expression, inhibited cell migratory capacity. Clinically, high levels of CXCR4 always correlated with metastasis and poor prognosis of CRC patients. In conclusion, LPS participate in the whole process of hepatic metastasis of CRC, not only causing liver damage resulting in the production of SDF-1α, but also enhancing the invasive potential of CRC cells by promoting CXCR4 expression and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Jing
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Han
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Fo-Bao
authors.initials: FB
authors.lastname: Lai
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Zeng
authors.affiliation: b Oncology Department , Ji'an Hospital, Shanghai East Hospital, Tongji University School of Medicine , Shanghai , China.
authors.forename: Guo-Feng
authors.initials: GF
authors.lastname: Yu
authors.affiliation: c Ultrasonography Department , The First Affiliated Hospital of Soochow University , Jiangsu , China.
authors.forename: Qing-Min
authors.initials: QM
authors.lastname: Fan
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Qiu-Dong
authors.initials: QD
authors.lastname: Zhao
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Meng-Chao
authors.initials: MC
authors.lastname: Wu
authors.affiliation: a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Wei
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008297:Male; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D054377:Chemokine CXCL12; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019718:Receptors, CXCR4
keywords: NF-κB; SDF-1α/CXCR4 axis; colorectal cancer; epithelial-mesenchymal transition; lipopolysaccharides