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

TY - JOUR

T1 - HRG/HER2/HER3 signaling promotes AhR-mediated Memo-1 expression and migration in colorectal cancer

AU - Bogoevska, V

AU - Wolters-Eisfeld, G

AU - Hofmann, B T

AU - El Gammal, A T

AU - Mercanoglu, B

AU - Gebauer, F

AU - Vashist, Y K

AU - Bogoevski, D

AU - Perez, D

AU - Gagliani, N

AU - Izbicki, J R

AU - Bockhorn, M

AU - Güngör, C

PY - 2017/4/27

Y1 - 2017/4/27

N2 - 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.Oncogene advance online publication, 12 December 2016; doi:10.1038/onc.2016.390.

AB - 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.Oncogene advance online publication, 12 December 2016; doi:10.1038/onc.2016.390.

U2 - 10.1038/onc.2016.390

DO - 10.1038/onc.2016.390

M3 - SCORING: Journal article

C2 - 27941874

VL - 36

SP - 2394

EP - 2404

JO - ONCOGENE

JF - ONCOGENE

SN - 0950-9232

IS - 17

ER -