title: Relocation of CLIC1 promotes tumor cell invasion and colonization of fibrin.
abstract: Chloride intracellular channel 1 (CLIC1) has been shown to be upregulated in various malignancies but its exact function remains unclear. Here, it is revealed that CLIC1 is critical for the stability of invadopodia in endothelial and tumor cells embedded in a 3-dimensional (3D) matrix of fibrin. Invadopodia stability was associated with the capacity of CLIC1 to induce stress fiber and fibronectin matrix formation following its β3 integrin (ITGB3)-mediated recruitment into invadopodia. This pathway, in turn, was relevant for fibrin colonization as well as slug (SNAI2) expression and correlated with a significant role of CLIC1 in metastasis in vivo. Mechanistically, a reduction of myosin light chain kinase (MYLK) in CLIC1-depleted as well as β3 integrin-depleted cells suggests an important role of CLIC1 for integrin-mediated actomyosin dynamics in cells embedded in fibrin. Overall, these results indicate that CLIC1 is an important contributor to tumor invasion, metastasis, and angiogenesis.
  
  
  CONCLUSIONS
  This study uncovers an important new function of CLIC1 in the regulation of cell-extracellular matrix interactions and ability of tumor cells to metastasize to distant organs.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Shadyside Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Gurski
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Shadyside Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Knowles
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Per H
authors.initials: PH
authors.lastname: Basse
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Shadyside Medical Center, Pittsburgh, Pennsylvania. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Maranchie
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Shadyside Medical Center, Pittsburgh, Pennsylvania. University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania. Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University Medical Center, Homburg, Saarland, Germany. Jan.Pilch@uniklinikum-saarland.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Pilch
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000473:pathology*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C501966:CLIC1 protein, human; D018118:Chloride Channels; C501967:Clic1 protein, mouse; C061248:ITGB3 protein, human; D039661:Integrin beta3; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors