{"doi":"10.1039/d5mo00111k","title":"Hypoxia-induced alterations in lipid polyunsaturation and associated proteins drive aggressive metastasis in pancreatic cancer\n                    <i>via</i>\n                    the PPAR/hypoxia pathway","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>In pancreatic ductal adenocarcinoma, hypoxia is a crucial component of the tumour microenvironment and is associated with worse clinical outcomes. Adaptation to extreme hypoxic settings is based on abnormal lipid metabolism, but insights into how hypoxia-regulated lipid changes link with aggressive migratory potential in pancreatic cancer are lacking. This study investigates the molecular processes, pathways, and critical proteins involved in hypoxia-induced lipidic and polyunsaturated fatty acid alterations in pancreatic cancer. Our findings elucidate increased multilayer unsaturation in FA chains of major lipid classes associated with greater migration and invasion, as well as higher abundances of particular desaturases. The expression of these proteins was verified in clinical tumour samples by unsaturated fatty acid biosynthesis-related gene enrichment score. High unsaturated fatty acid clusters were shown to be associated with a low survival rate. Pathway correlation and protein–protein interaction analysis indicated that the PPAR-hypoxia axis and SCD/FADS2/APOC3-HDLBP protein network are implicated in mediating the observed alterations in lipid pools and poly-unsaturation levels in pancreatic cancer under hypoxia. These results provide novel therapeutic targets in pancreatic cancer while improving our understanding of hypoxia-induced migratory potential in pancreatic cancer.</jats:p>\n                  <jats:p/>","journal":"Molecular Omics","year":2025,"id":627464,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1237919,"name":"Avinash Singh","orcid":"0000-0001-6572-6732","position":1,"is_corresponding":false},{"id":728336,"name":"Sanjeeva Srivastava","orcid":"0000-0001-5159-6834","position":2,"is_corresponding":false},{"id":371121,"name":"Shobhna Kapoor","orcid":"0000-0003-3684-4312","position":3,"is_corresponding":false},{"id":1624037,"name":"Prema Kumari Agarwala","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Hypoxia-induced alterations in lipid polyunsaturation and associated proteins drive aggressive metastasis in pancreatic cancer\n                    <i>via</i>\n                    the PPAR/hypoxia pathway","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>In pancreatic ductal adenocarcinoma, hypoxia is a crucial component of the tumour microenvironment and is associated with worse clinical outcomes. Adaptation to extreme hypoxic settings is based on abnormal lipid metabolism, but insights into how hypoxia-regulated lipid changes link with aggressive migratory potential in pancreatic cancer are lacking. This study investigates the molecular processes, pathways, and critical proteins involved in hypoxia-induced lipidic and polyunsaturated fatty acid alterations in pancreatic cancer. Our findings elucidate increased multilayer unsaturation in FA chains of major lipid classes associated with greater migration and invasion, as well as higher abundances of particular desaturases. The expression of these proteins was verified in clinical tumour samples by unsaturated fatty acid biosynthesis-related gene enrichment score. High unsaturated fatty acid clusters were shown to be associated with a low survival rate. Pathway correlation and protein–protein interaction analysis indicated that the PPAR-hypoxia axis and SCD/FADS2/APOC3-HDLBP protein network are implicated in mediating the observed alterations in lipid pools and poly-unsaturation levels in pancreatic cancer under hypoxia. These results provide novel therapeutic targets in pancreatic cancer while improving our understanding of hypoxia-induced migratory potential in pancreatic cancer.</jats:p>\n                  <jats:p/>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41186383","pmcid":null,"openalex_id":"https://openalex.org/W4415849771","authors":[],"funders":[{"funder_name":"Science and Engineering Research Board","grant_id":"Unassigned","title":null},{"funder_name":"Science and Engineering Research Board","grant_id":"","title":null},{"funder_name":"Science and Technology Program of Hunan Province","grant_id":"","title":null}],"total_grants":3,"fwci":1.4182,"citation_percentile":0.83271435,"influential_citations":0,"citation_trend":[{"year":2026,"count":3}],"oa_status":"closed","license":"http://rsc.li/journals-terms-of-use","oa_locations":[{"url":"https://academic.oup.com/molecular-omics/article-pdf/21/6/736/66636874/d5mo00111k.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1039/d5mo00111k","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41186383","host_type":"repository"}],"fields_of_study":["Cancer, Lipids, and Metabolism","Cancer, Hypoxia, and Metabolism","Lipid metabolism and biosynthesis","Humans","Pancreatic Neoplasms","Lipid Metabolism","Fatty Acids, Unsaturated","Tumor Microenvironment","Peroxisome Proliferator-Activated Receptors","Gene Expression Regulation, Neoplastic","Hypoxia","Signal Transduction","Carcinoma, Pancreatic Ductal","Protein Interaction Maps","Neoplasm Metastasis","Cell Line, Tumor","Cell Movement"],"mesh_terms":["Hypoxia","Cell Movement","Fatty Acids, Unsaturated","Humans","Neoplasm Metastasis","Pancreatic Neoplasms","Signal Transduction","Gene Expression Regulation, Neoplastic","Carcinoma, Pancreatic Ductal","Cell Line, Tumor","Peroxisome Proliferator-Activated Receptors","Lipid Metabolism","Tumor Microenvironment","Protein Interaction Maps"],"keywords":["Pancreatic cancer","Metastasis","Hypoxia (environmental)","Fatty acid","microRNA","Lipid metabolism","Polyunsaturated fatty acid","Cancer"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T17:35:45.212339Z","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":[]}