Your browser doesn't support javascript.
loading
ATF2 loss promotes tumor invasion in colorectal cancer cells via upregulation of cancer driver TROP2.
Huebner, Kerstin; Erlenbach-Wuensch, Katharina; Prochazka, Jan; Sheraj, Ilir; Hampel, Chuanpit; Mrazkova, Blanka; Michalcikova, Tereza; Tureckova, Jolana; Iatsiuk, Veronika; Weissmann, Anne; Ferrazzi, Fulvia; Kunze, Philipp; Nalli, Enise; Sammer, Elisabeth; Gehring, Annemarie; Cheema, Marie M; Eckstein, Markus; Paap, Eva-Maria; Soederberg, Agnes; Fischer, Corinna; Paul, Sushmita; Mahadevan, Vijayalakshmi; Ndreshkjana, Benardina; Meier, Melanie A; Muehlich, Susanne; Geppert, Carol I; Merkel, Susanne; Grutzmann, Robert; Roehe, Adriana; Banerjee, Sreeparna; Hartmann, Arndt; Sedlacek, Radislav; Schneider-Stock, Regine.
Afiliación
  • Huebner K; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Erlenbach-Wuensch K; Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
  • Prochazka J; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Sheraj I; Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.
  • Hampel C; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Mrazkova B; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Michalcikova T; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Tureckova J; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Iatsiuk V; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Weissmann A; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Ferrazzi F; Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
  • Kunze P; Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Nalli E; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Sammer E; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Gehring A; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Cheema MM; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Eckstein M; Czech Center for Phenogenomics, Institute of Molecular Genetics of the ASCR, v.v.i, 142 20, Prague, Czech Republic.
  • Paap EM; Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
  • Soederberg A; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Fischer C; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Paul S; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Mahadevan V; Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Jodhpur, 342037, India.
  • Ndreshkjana B; Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, 560100, India.
  • Meier MA; Experimental Tumor Pathology, Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), Universitätsstraße 22, 91054, Erlangen, Germany.
  • Muehlich S; Department of Chemistry and Pharmacy, Molecular and Clinical Pharmacy, Friedrich Alexander University Erlangen-Nürnberg, 91058, Erlangen, Germany.
  • Geppert CI; Department of Chemistry and Pharmacy, Molecular and Clinical Pharmacy, Friedrich Alexander University Erlangen-Nürnberg, 91058, Erlangen, Germany.
  • Merkel S; Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
  • Grutzmann R; Department of Surgery, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Roehe A; Department of Surgery, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Banerjee S; Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg, 91054, Erlangen, Germany.
  • Hartmann A; Department of Pathology and Legal Medicine, Federal University of Health Sciences of Porto Alegre, Porto Alegre, 90050-170, Brazil.
  • Sedlacek R; Department of Biological Sciences, Middle East Technical University, 06800, Ankara, Turkey.
  • Schneider-Stock R; Institute of Pathology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nürnberg (FAU), 91054, Erlangen, Germany.
Cell Mol Life Sci ; 79(8): 423, 2022 Jul 15.
Article en En | MEDLINE | ID: mdl-35838828
In cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients. NanoString gene expression and ChIP analysis confirmed trophoblast cell surface antigen 2 (TROP2) as a novel inhibitory ATF2 target gene. This inverse correlation was further observed in primary human tumor tissues. Immunostainings revealed that high intratumoral heterogeneity for ATF2 and TROP2 expression was sustained also in liver metastasis. Mechanistically, our in vitro data of CRISPR/Cas9-generated ATF2 knockout (KO) clones revealed that high TROP2 levels were critical for cell de-adhesion and increased cell migration without triggering EMT. TROP2 was enriched in filopodia and displaced Paxillin from adherens junctions. In vivo imaging, micro-computer tomography, and immunostainings verified that an ATF2KO/TROP2high status triggered tumor invasiveness in in vivo mouse and chicken xenograft models. In silico analysis provided direct support that ATF2low/TROP2high expression status defined high-risk CRC patients. Finally, our data demonstrate that ATF2 acts as a tumor suppressor by inhibiting the cancer driver TROP2. Therapeutic TROP2 targeting might prevent particularly the first steps in metastasis, i.e., the de-adhesion and invasion of colon cancer cells.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Factor de Transcripción Activador 2 / Antígenos de Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Factor de Transcripción Activador 2 / Antígenos de Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza