{"doi":"10.1101/2021.05.17.444471","title":"Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells","abstract":"Abstract Tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either TSC1 or TSC2 . Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking upregulation of Interleukin-6 (IL-6). LAM patient plasma contained increased circulating IL-6 compared with healthy controls, and TSC2-deficient cells showed upregulation of IL-6 transcription and secretion compared to wildtype cells. IL-6 blockade repressed the proliferation and migration of TSC2-deficient cells and reduced oxygen consumption and extracellular acidification. U- 13 C glucose tracing revealed that IL-6 knockout reduced 3-phosphoserine and serine production in TSC2-deficient cells, implicating IL-6 in de novo serine metabolism. IL-6 knockout reduced expression of phosphoserine aminotransferase 1 (PSAT1), an essential enzyme in serine biosynthesis. Importantly, recombinant IL-6 treatment rescued PSAT1 expression in the TSC2-deficient, IL-6 knockout clones selectively and had no effect on wildtype cells. Treatment with anti-IL-6 (aIL-6) antibody similarly reduced cell proliferation and migration and reduced renal tumors in Tsc2 +/- mice, while reducing PSAT1 expression. These data reveal a novel mechanism through which IL-6 regulates serine biosynthesis, with potential relevance to the therapy of tumors with mTORC1 hyperactivity. Classification Major category: Biological Sciences Minor category: Cell Biology","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220724,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":753112,"name":"Harilaos Filippakis","orcid":null,"position":1,"is_corresponding":false},{"id":753111,"name":"Thomas R. Hougard","orcid":null,"position":2,"is_corresponding":false},{"id":298781,"name":"Heng Du","orcid":"0000-0001-9067-0910","position":3,"is_corresponding":false},{"id":820409,"name":"Chenyang Ye","orcid":"0000-0002-3695-6309","position":4,"is_corresponding":false},{"id":758867,"name":"Heng-Jia Liu","orcid":"0000-0001-9685-6572","position":5,"is_corresponding":false},{"id":752546,"name":"Long Zhang","orcid":"0000-0003-4710-9946","position":6,"is_corresponding":false},{"id":820926,"name":"K.M. Hindi","orcid":null,"position":7,"is_corresponding":false},{"id":415512,"name":"Shefali Bagwe","orcid":"0009-0007-2183-2040","position":8,"is_corresponding":false},{"id":706674,"name":"Julie Nijmeh","orcid":"0000-0002-4392-6263","position":9,"is_corresponding":false},{"id":3257,"name":"John M. Asara","orcid":"0000-0001-7450-2589","position":10,"is_corresponding":false},{"id":305998,"name":"Wei Shi","orcid":"0000-0001-6499-2473","position":11,"is_corresponding":false},{"id":320051,"name":"Souheil El‐Chemaly","orcid":"0000-0003-2929-5589","position":12,"is_corresponding":false},{"id":247628,"name":"Elizabeth P. Henske","orcid":"0000-0001-7978-6699","position":13,"is_corresponding":false},{"id":573808,"name":"Hilaire C. Lam","orcid":"0000-0003-4887-3161","position":14,"is_corresponding":false},{"id":820408,"name":"Ji Wang","orcid":"0000-0002-7771-5819","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:53:50.838581Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}