{"doi":"10.26508/lsa.201900481","title":"The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer","abstract":"The gut barrier separates trillions of microbes from the largest immune system in the body; when compromised, a \"leaky\" gut barrier fuels systemic inflammation, which hastens the progression of chronic diseases. Strategies to detect and repair the leaky gut barrier remain urgent and unmet needs. Recently, a stress-polarity signaling (SPS) pathway has been described in which the metabolic sensor, AMP-kinase acts via its effector, GIV (also known as Girdin) to augment epithelial polarity exclusively under energetic stress and suppresses tumor formation. Using murine and human colon-derived organoids, and enteroid-derived monolayers (EDMs) that are exposed to stressors, we reveal that the SPS-pathway is active in the intestinal epithelium and requires a catalytically active AMP-kinase. Its pharmacologic augmentation resists stress-induced collapse of the epithelium when challenged with microbes or microbial products. In addition, the SPS-pathway is suppressed in the aging gut, and its reactivation in enteroid-derived monolayers reverses aging-associated inflammation and loss of barrier function. It is also silenced during progression of colorectal cancers. These findings reveal the importance of the SPS-pathway in the gut and highlights its therapeutic potential for treating gut barrier dysfunction in aging, cancer, and dysbiosis.","journal":"Life Science Alliance","year":2020,"id":93605,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9529,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":467348,"name":"Lee Swanson","orcid":"0000-0002-1201-1298","position":1,"is_corresponding":false},{"id":348398,"name":"Ibrahim M. Sayed","orcid":"0000-0001-8207-6401","position":2,"is_corresponding":false},{"id":467349,"name":"Yash Mittal","orcid":"0000-0003-1962-4000","position":3,"is_corresponding":false},{"id":467350,"name":"Blaze B. C. Lim","orcid":"0000-0002-7980-8584","position":4,"is_corresponding":false},{"id":468505,"name":"Stella‐Rita Ibeawuchi","orcid":null,"position":5,"is_corresponding":false},{"id":467351,"name":"Marc Foretz","orcid":"0000-0001-7017-9032","position":6,"is_corresponding":false},{"id":467352,"name":"Benoı̂t Viollet","orcid":"0000-0002-0121-0224","position":7,"is_corresponding":false},{"id":294966,"name":"Debashis Sahoo","orcid":"0000-0003-2329-8228","position":8,"is_corresponding":false},{"id":348404,"name":"Soumita Das","orcid":"0000-0003-3895-3643","position":9,"is_corresponding":false},{"id":294967,"name":"Pradipta Ghosh","orcid":"0000-0002-8917-3201","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-18T22:31:34.149524Z","pmid":"32041849","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":[]}