Journal article

Publication year: 2014

Pages: 198-207

Journal: Cellular Signalling

Volume number: 26

Issue number: 2

ISSN: 0898-6568

eISSN: 1873-3913

DOI Link: https://doi.org/10.1016/j.cellsig.2013.11.001

Publisher: Elsevier

Abstract: 

Flotillins are highly conserved and widely spread proteins that function in receptor tyrosine kinase signaling and membrane trafficking processes. Flotillin-1 and flotillin-2 have been shown to form both homo- and hetero-oligomers, and their cellular localization changes during signaling. Increased expression of flotillins has been detected in several types of cancer and shown to correlate with poor survival. Consistently, flotillin-2 knockout mice show a reduced formation of metastases in a breast cancer animal model. Our recent data have shown that flotillin-1 depletion results in diminished activation of the epidermal growth factor receptor and impairs its downstream signaling towards the mitogen activated protein kinases and the respective transcriptional response. Here we show that genetic ablation of flotillin-2 in a mouse model or its knockdown in cultured cells increases extracellular signal regulated kinase (ERR) activation. Furthermore, the downstream transcriptional targets of ERK and p53 are upregulated at both mRNA and protein levels. These data suggest that opposite effects are obtained upon ablation of one of the two flotillins, with flotillin-2 knockout/knockdown enhancing and flotillin-1 knockdown inhibiting ERR signaling. Due to their overexpression in cancers, flotillins may be considered as cancer therapy targets. However, our findings suggest that care needs to be taken when interfering with flotillin function, as undesired effects such as deregulation of growth-associated genes may emerge in certain cell types.

Harvard Citation style: Banning, A., Regenbrecht, C. and Tikkanen, R. (2014) Increased activity of mitogen activated protein kinase pathway in flotillin-2 knockout mouse model, Cellular Signalling, 26(2), pp. 198-207. https://doi.org/10.1016/j.cellsig.2013.11.001

APA Citation style: Banning, A., Regenbrecht, C., & Tikkanen, R. (2014). Increased activity of mitogen activated protein kinase pathway in flotillin-2 knockout mouse model. Cellular Signalling. 26(2), 198-207. https://doi.org/10.1016/j.cellsig.2013.11.001