title: ERα17p, an ERα P295 -T311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements.
abstract: Recently, our knowledge on estrogen receptor alpha (ERα) functions and fate has progressed: ERα enters in repeated transcription-modulating cycles (nucleus/cytoplasm/membrane trafficking processes and proteasomal degradation) that are governed by specific protein-protein interactions. Receptor fragments, especially those resulting from the proteolysis of its ligand binding domain, as well as corresponding synthetic peptides, have been studied with respect to their estrogenic/antiestrogenic potency. A peptide, corresponding to the human ERα P(295) -T(311) sequence (ERα17p) has been shown to alter breast cancer cell fate, triggering proliferation, or apoptosis. The aim of this work was to explore the effect of ERα17p on breast cancer cell migration and actin cytoskeleton dynamics and further analyze the mechanism of its membrane action. We show that ERα17p increases (MCF-7 and SK-BR-3 cells) or decreases (T47D and MDA-MB-231 cells) migration of breast cancer cells, in an ERα-independent manner, by mechanism(s) depending on Rho/ROCK and PI3K/Akt signaling pathways. Moreover, the peptide enhances the association of both estrogens and androgens to membranes and modifies cell migration, induced by E(2) -BSA. Additionally, initial evidence of a possible agonistic action of the peptide on GPR30 is also provided. ERα17p can be considered as a cell migration-modulator and could therefore constitute a therapeutic challenge, even in anti-estrogen-resistant tumors.
authors.affiliation: Laboratory of Experimental Endocrinology, School of Medicine University of Crete, Heraklion, Greece.
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Pelekanou
authors.forename: Dominique
authors.initials: D
authors.lastname: Gallo
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Maria
authors.initials: M
authors.lastname: Troullinaki
authors.forename: Iosif
authors.initials: I
authors.lastname: Pediaditakis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Charalampopoulos
authors.forename: Yves
authors.initials: Y
authors.lastname: Jacquot
authors.forename: Guy
authors.initials: G
authors.lastname: Leclercq
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000199:Actins / Q000378:metabolism*; D001704:Biopolymers / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis / Q000473:pathology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000199:Actins; D001704:Biopolymers; D047628:Estrogen Receptor alpha