Mediator of ERBB2-driven cell motility (MEMO) promotes extranuclear estrogen receptor signaling involving the growth factor receptors IGF1R and ERBB2.

J Biol Chem 2013 Aug 16;288(34):24590-9. Epub 2013 Jul 16.

Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.

In addition to nuclear estrogen receptor (ER) acting as a transcription factor, extranuclear ER also plays an important role in cancer cell growth regulation through activation of kinase cascades. However, the molecular mechanisms by which extranuclear ER exerts its function are still poorly understood. Here, we report that mediator of ERBB2-driven cell motility (MEMO) regulates extranuclear functions of ER. MEMO physically and functionally interacted with ER. Through its interaction with the growth factor receptors IGF1R and ERBB2, MEMO mediated extranuclear functions of ER, including activation of mitogen-activated protein kinase (MAPK) and protein kinase B/AKT, two important growth regulatory protein kinases, and integration of function with nuclear ER. Activation of MAPK and AKT was responsible for MEMO modulation of ER phosphorylation and estrogen-responsive gene expression. Moreover, MEMO increased anchorage-dependent and -independent growth of ER-positive breast cancer cells in vitro and was required for estrogen-induced breast tumor growth in nude mice. Together, our studies identified MEMO as a new component of extranuclear ER signalosome and suggest an essential role for MEMO in the regulation of ER-positive breast cancer cell growth.

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.M113.467837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3750157PMC
August 2013
23 Reads

Publication Analysis

Top Keywords

breast cancer
8
factor receptors
8
protein kinase
8
igf1r erbb2
8
extranuclear functions
8
growth factor
8
estrogen receptor
8
er-positive breast
8
receptors igf1r
8
erbb2-driven cell
8
cancer cell
8
mediator erbb2-driven
8
cell growth
8
cell motility
8
motility memo
8
memo
8
growth
7
extranuclear
6
growth regulatory
4
regulatory protein
4

References

(Supplied by CrossRef)
Scaffolding proteins mediating membrane-initiated extranuclear actions of estrogen receptor
Boonyaratanakornkit et al.
Steroids 2011

Similar Publications