title: CD147 promotes Src-dependent activation of Rac1 signaling through STAT3/DOCK8 during the motility of hepatocellular carcinoma cells.
abstract: Metastasis is considered a dynamic process in tumor development that is related to abnormal migration and invasion. Tumor cells can move as individual cells in two interconvertible modes: mesenchymal-type and amoeboid. Previously, we reported that the interaction between CD147 and Annexin II can inhibit the amoeboid movement in hepatocellular carcinoma (HCC) cells. However, the mechanism of CD147 involved in mesenchymal movement is still unclear. Notably, our results show overexpression of CD147 led to mesenchymal-type movement in HCC cells. Evidence indicated that the mesenchymal-type cell movement induced by CD147 was Src dependent, as observed by confocal microscopy and Rac1 activity assay. The phosphorylation of Src (pY416-Src) can be up-regulated by CD147, and this regulation is mediated by focal adhesion kinase (FAK). Next, we identified DOCK8 as a GEF for Rac1, a key molecule driving mesenchymal-type movement. We also found that Src promotes STAT3 phosphorylation and STAT3 facilitates DOCK8 transcription, thus enhancing DOCK8 expression and Rac1 activation. This study provides a novel mechanism of CD147 regulating mesenchymal-type movement in HCC cells.
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Hong-Yong
authors.initials: HY
authors.lastname: Cui
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Liu
authors.affiliation: College of Life and Health Sciences, Northeastern University, Shenyang, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Fu
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Zhi-Nan
authors.initials: ZN
authors.lastname: Chen
authors.affiliation: Cell Engineering Research Center & Department of Cell Biology, State Key Laboratory of Cancer Biology, National Key Discipline of Cell Biology, Fourth Military Medical University, Xi'an, China.
authors.forename: Jian-Li
authors.initials: JL
authors.lastname: Jiang
mesh_terms: D051926:Basigin / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018613:Microscopy, Confocal; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: C497886:BSG protein, human; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; C107953:RAC1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051926:Basigin; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein