title: HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer.
abstract: Colorectal cancer (CRC) is a complex disease with still unsatisfactory prognosis even in western societies, although substantial progress has been made in pre-screening programs, surgical techniques and targeted therapy options. Mediator of motility-1 (Memo-1) was previously recognized as an important effector of cell migration downstream of receptor tyrosine kinase signaling in breast cancer. This study identified Memo-1 as frequently overexpressed in CRC and established a close link between extracellular HER2 activation, AhR/ARNT transcriptional activity and Memo-1 expression. Dissection of the hMemo-1 gene promoter using reporter assays and chromatin IP techniques revealed recruitment of Aryl hydrocarbon receptor (AhR)/Aryl hydrocarbon receptor nuclear-translocator (ARNT) complex, which positively influenced Memo-1 expression in cancer cells. We found that Memo-1 depletion negatively influenced the cellular actin network and that its expression is required for HER2-mediated cell migration and invasion. Moreover, analyses of Memo-1 expression in primary CRC revealed correlation with clinical parameters that point to Memo-1 as a new prognostic factor of aggressive disease in CRC patients. Altogether, these observations demonstrate that Memo-1 is an important downstream regulator of HER2-driven CRC cell migration and invasion through connecting extracellular signals from membrane to the cytoskeletal actin network.
authors.affiliation: Cardiologicum Hamburg Research and Study Center, Hamburg, Germany.|Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Bogoevska
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Wolters-Eisfeld
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: B T
authors.initials: BT
authors.lastname: Hofmann
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A T
authors.initials: AT
authors.lastname: El Gammal
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Mercanoglu
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Gebauer
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Surgery, Section for Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland.
authors.forename: Y K
authors.initials: YK
authors.lastname: Vashist
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Bogoevski
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Perez
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gagliani
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Bockhorn
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Güngör
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000473:pathology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009361:Neoplasm Invasiveness; D019159:Nonheme Iron Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D015398:Signal Transduction; D000099053:Histidine-Rich Glycoprotein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019159:Nonheme Iron Proteins; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D018336:Receptors, Aryl Hydrocarbon; D000099053:Histidine-Rich Glycoprotein; C527585:MEMO1 protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human