{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Domenico Memoli"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-6120"],"description":["Adipose tissue is a metabolic and endocrine organ that secretes numerous bioactive molecules called adipocytokines. Among these, adiponectin has been argued to have a crucial role in obesity-associated breast cancer. The key molecule of adiponectin signaling is AMP-activated protein kinase (AMPK), mainly activated by Liver Kinase B1 (LKB1).  Here, we demonstrated how the ERalfa/LKB1 interaction may negatively interfere with the capability of LKB1 to phosphorylate AMPK and then inhibit its downstream signaling TSC2/mTOR/p70S6k.  In MCF-7 cells upon adiponectin AMPK signaling was not working, keeping its downstream protein Acetyl-CoA Carboxylase (ACC) still active. In contrast, in MDA-MB-231 cells the phosphorylation of AMPK and ACC was enhanced with consequent inhibition of both lipogenesis and cell growth. Thus, upon adiponectin, ERalfa signaling switched the energy balance of breast cancer cells towards a lipogenic phenotype. In other words, adiponectin in all the concentrations tested played an inhibitory role on ERalpha-negative breast cancer cell growth and progression either in vitro or in vivo. In contrast, low adiponectin levels, similar to those circulating in obese patients, worked on ERalfa-positive cells as a growth factor, stimulating their growth and progression. The latter effect seems to be blunted in vivo only in the presence of high adiponectin concentration.  Based on the present results, it can be concluded that if we prospectively address adiponectin as a pharmacological tool, a separate therapeutic treatment should be carefully assessed in ERalfa-positive and negative breast-cancer patients."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sequencing - TruSeq mRNA Sample Prep Kit (Illumina)","Sample Collection - Human MCF-7 and MDA-MB-231 breast cancer epithelial cells were obtained from American Type Culture Collection (Manassas, VA, USA). MCF-7 and MDA-MB-231 cells untreated or treated with adiponectin (5 and 30 µg/ml) for 24 h","Nucleic Acid Extraction - Total RNA","Sample Treatment - Adiponectina","Library Construction - TruSeq mRNA Sample Prep Kit (Illumina)"],"figure_sub":["Organization","MINSEQE Score","Assays and Data","MAGE-TAB Files"],"data_protocol":["Sequence Alignment - Illumina Sequecing"],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina HiSeq 2500"],"study_type":["RNA-seq of coding RNA"],"species":["Homo sapiens"],"pubmed_authors":["Domenico Memoli"],"additional_accession":[]},"is_claimable":false,"name":"Uncoupling effects of ERalfa on LKB1/AMPK interaction upon adiponectin exposure in breast cancer","description":"Adipose tissue is a metabolic and endocrine organ that secretes numerous bioactive molecules called adipocytokines. Among these, adiponectin has been argued to have a crucial role in obesity-associated breast cancer. The key molecule of adiponectin signaling is AMP-activated protein kinase (AMPK), mainly activated by Liver Kinase B1 (LKB1).  Here, we demonstrated how the ERalfa/LKB1 interaction may negatively interfere with the capability of LKB1 to phosphorylate AMPK and then inhibit its downstream signaling TSC2/mTOR/p70S6k.  In MCF-7 cells upon adiponectin AMPK signaling was not working, keeping its downstream protein Acetyl-CoA Carboxylase (ACC) still active. In contrast, in MDA-MB-231 cells the phosphorylation of AMPK and ACC was enhanced with consequent inhibition of both lipogenesis and cell growth. Thus, upon adiponectin, ERalfa signaling switched the energy balance of breast cancer cells towards a lipogenic phenotype. In other words, adiponectin in all the concentrations tested played an inhibitory role on ERalpha-negative breast cancer cell growth and progression either in vitro or in vivo. In contrast, low adiponectin levels, similar to those circulating in obese patients, worked on ERalfa-positive cells as a growth factor, stimulating their growth and progression. The latter effect seems to be blunted in vivo only in the presence of high adiponectin concentration.  Based on the present results, it can be concluded that if we prospectively address adiponectin as a pharmacological tool, a separate therapeutic treatment should be carefully assessed in ERalfa-positive and negative breast-cancer patients.","dates":{"release":"2020-02-27T00:00:00Z","modification":"2022-02-07T23:19:31.571Z","creation":"2022-02-07T23:19:31.571Z"},"accession":"E-MTAB-6120","cross_references":{"ENA":["ERP120059"],"EFO":["EFO_0002944","EFO_0004170","EFO_0004917","EFO_0005518","EFO_0003738","EFO_0003969","EFO_0004184"]}}