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HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer

Oncogene volume 36, pages 2394–2404 (2017)Cite this article

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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.

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Acknowledgements

We thank A Heinecke, P Merkert and P Schröder for excellent technical assistance and Dr M Linnebacher for providing primary CRC cells. This work (CG) was partially funded by the ‘Roggenbuck Foundation’, Hamburg, Germany.

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Authors and Affiliations

  1. Cardiologicum Hamburg Research and Study Center, Hamburg, Germany

    V Bogoevska

  2. Department of General, Visceral and Thoracic Surgery, Experimental Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    V Bogoevska, G Wolters-Eisfeld, B T Hofmann, A T El Gammal, B Mercanoglu, F Gebauer, Y K Vashist, D Bogoevski, D Perez, N Gagliani, J R Izbicki, M Bockhorn & C Güngör

  3. Department of Surgery, Section for Visceral Surgery, Kantonsspital Aarau AG, Aarau, Switzerland

    Y K Vashist

  4. Department of Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany

    N Gagliani

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Correspondence to C Güngör.

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Bogoevska, V., Wolters-Eisfeld, G., Hofmann, B. et al. HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer. Oncogene 36, 2394–2404 (2017). https://doi.org/10.1038/onc.2016.390

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