{"doi":"10.1002/hep.32797","title":"Melanoma differentiation associated gene‐9/syndecan binding protein promotes hepatocellular carcinoma","abstract":"BACKGROUND AND AIMS: The oncogene Melanoma differentiation associated gene-9/syndecan binding protein (MDA-9/SDCBP) is overexpressed in many cancers, promoting aggressive, metastatic disease. However, the role of MDA-9 in regulating hepatocellular carcinoma (HCC) has not been well studied. APPROACH AND RESULTS: To unravel the function of MDA-9 in HCC, we generated and characterized a transgenic mouse with hepatocyte-specific overexpression of MDA-9 (Alb/MDA-9). Compared with wild-type (WT) littermates, Alb/MDA-9 mice demonstrated significantly higher incidence of N-nitrosodiethylamine/phenobarbital-induced HCC, with marked activation and infiltration of macrophages. RNA sequencing (RNA-seq) in naive WT and Alb/MDA-9 hepatocytes identified activation of signaling pathways associated with invasion, angiogenesis, and inflammation, especially NF-κB and integrin-linked kinase signaling pathways. In nonparenchymal cells purified from naive livers, single-cell RNA-seq showed activation of Kupffer cells and macrophages in Alb/MDA-9 mice versus WT mice. A robust increase in the expression of Secreted phosphoprotein 1 (Spp1/osteopontin) was observed upon overexpression of MDA-9. Inhibition of NF-κB pathway blocked MDA-9-induced Spp1 induction, and knock down of Spp1 resulted in inhibition of MDA-9-induced macrophage migration, as well as angiogenesis. CONCLUSIONS: Alb/MDA-9 is a mouse model with MDA-9 overexpression in any tissue type. Our findings unravel an HCC-promoting role of MDA-9 mediated by NF-κB and Spp1 and support the rationale of using MDA-9 inhibitors as a potential treatment for aggressive HCC.","journal":"Hepatology","year":2022,"id":259077,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":911168,"name":"Saranya Chidambaranathan Reghupaty","orcid":"0000-0001-6660-1296","position":1,"is_corresponding":false},{"id":911799,"name":"Maria Del Carmen Camarena","orcid":null,"position":2,"is_corresponding":false},{"id":911800,"name":"Rachel G. Mendoza","orcid":null,"position":3,"is_corresponding":false},{"id":330318,"name":"Mark A. Subler","orcid":null,"position":4,"is_corresponding":false},{"id":344255,"name":"Jennifer E. Koblinski","orcid":"0000-0002-7156-2030","position":5,"is_corresponding":false},{"id":274831,"name":"Rebecca Martin","orcid":"0000-0001-9948-5463","position":6,"is_corresponding":false},{"id":265858,"name":"Mikhail G. Dozmorov","orcid":"0000-0002-0086-8358","position":7,"is_corresponding":false},{"id":291514,"name":"Nitai D. Mukhopadhyay","orcid":"0000-0002-1530-9516","position":8,"is_corresponding":false},{"id":437424,"name":"Jinze Liu","orcid":"0000-0003-0555-9412","position":9,"is_corresponding":false},{"id":578183,"name":"Xufeng Qu","orcid":null,"position":10,"is_corresponding":false},{"id":282003,"name":"Swadesh K. Das","orcid":"0000-0002-9605-9327","position":11,"is_corresponding":false},{"id":263243,"name":"Zhao Lai","orcid":"0000-0002-3543-5376","position":12,"is_corresponding":false},{"id":329122,"name":"Jolene J. Windle","orcid":"0000-0001-6690-385X","position":13,"is_corresponding":false},{"id":282004,"name":"Paul B. Fisher","orcid":"0000-0002-0085-4546","position":14,"is_corresponding":false},{"id":282002,"name":"Devanand Sarkar","orcid":"0000-0003-0973-2323","position":15,"is_corresponding":false},{"id":911167,"name":"Debashri Manna","orcid":"0000-0002-3111-7442","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:25:47.305414Z","pmid":"36120720","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":[]}