title: Mediator of ERBB2-driven cell motility (MEMO) promotes extranuclear estrogen receptor signaling involving the growth factor receptors IGF1R and ERBB2.
abstract: 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.
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing 100850, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.forename: Shibin
authors.initials: S
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Ning
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
authors.forename: Lisheng
authors.initials: L
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Junjian
authors.initials: J
authors.lastname: Huang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D019159:Nonheme Iron Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D047908:Intracellular Signaling Peptides and Proteins; D019159:Nonheme Iron Proteins; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D011960:Receptors, Estrogen; C527585:MEMO1 protein, human; C508053:ERBB2 protein, human
keywords: Breast Cancer; Cell Proliferation; ERBB2; Estrogen Receptor; Growth Factors; IGF1R; MEMO; Signal Transduction