title: LKB1 when associated with methylatedERα is a marker of bad prognosis in breast cancer.
abstract: Although the presence of nuclear estrogen receptor is widely used to guide breast cancer therapy, less attention has been paid to the receptor cytoplasmic signaling. Recently, we have shown that this pathway is operative in vivo and is activated in aggressive tumors representing a new potential target for breast cancer therapy. Here, we identified LKB1 as a partner of ERα and we explored its potential role in estrogen nongenomic signaling. The associations between LKB1 expression and the actors of this pathway, namely the methylated form of ERα (metERα), Src and PI3K, have been analyzed both in cultured cells and in 154 primary breast tumor samples. We found that LKB1 is a component of the cytoplasmic signaling complex in breast cell lines as well as in primary breast tumors. Moreover, an inverse correlation between the localization of LKB1 in nuclear and cytoplasmic compartments is observed. Importantly, high expression of cytoplasmic LKB1 is an independent marker of poor prognosis, associated with reduced overall survival (OS) and disease free survival (DFS). Conversely, the presence of nuclear LKB1 associates with increased OS and DFS. In conclusion, our results highlight that LKB1 expression in breast cancer appears to have opposite effects depending on its subcellular localization and may be used as a new prognostic biomarker.
authors.affiliation: Université de Lyon, France; Université Lyon 1, France; Inserm U1052, Centre de Recherche en Cancérologie de Lyon, France; CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, France; Equipe Labellisée "La Ligue", Lyon, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Bouchekioua-Bouzaghou
authors.forename: Coralie
authors.initials: C
authors.lastname: Poulard
authors.forename: Juliette
authors.initials: J
authors.lastname: Rambaud
authors.forename: Emilie
authors.initials: E
authors.lastname: Lavergne
authors.forename: Nader
authors.initials: N
authors.lastname: Hussein
authors.forename: Marc
authors.initials: M
authors.lastname: Billaud
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chabaud
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mader
authors.forename: Guila
authors.initials: G
authors.lastname: Dayan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Laura
authors.initials: L
authors.lastname: Corbo
authors.forename: Muriel
authors.initials: M
authors.lastname: Le Romancer
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008745:Methylation; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D019061:src-Family Kinases; C506487:ESR1 protein, human; C109790:STK11 protein, human
keywords: LKB1; biomarker; breast cancer; estrogen receptor α; estrogen signaling