{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T01:30:27Z","timestamp":1782955827502,"version":"3.54.5"},"reference-count":61,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Triple\u2010negative breast cancer (TNBC) exhibits altered lipid metabolism, driven by the tumor microenvironment's cancer\u2010associated fibroblasts (CAFs) and tumor\u2010associated macrophages (TAMs). CD36, a fatty acid translocase, is crucial in this metabolic adaptation of cancer cells. Despite its importance, what controls CD36\u2010mediated lipid flow is still unclear. This study identifies metadherin (MTDH), an oncogene, as a critical regulator of CD36\u2010dependent lipid exchange and TNBC progression. Using engineered spheroid models that mimic tumor microenvironment with MTDH\u2010Wt and MTDH\u03947 overexpressing TNBC cells co\u2010cultured with CAFs and TAMs, we observed increased lipid uptake, enhanced EMT, and aggressive metastatic features driven by MTDH\u2010CD36 signaling. Further analyses, including advanced microscopy and transcriptomics, revealed that MTDH\u03947 overexpression in TNBC cells in the presence of stromal\u2010immune cells, amplifies lipid metabolic pathways, promotes stemness, and pro\u2010metastatic signaling. Intriguingly, increased formation of tunnelling nanotube\u2010like structures, indicative of metabolic rewiring, was observed in Lv.MTDH\u03947\u2010MDA\u2010MB\u2010231\n                    <jats:sup>CAF\u2010TAM<\/jats:sup>\n                    heterotypic spheroids. These changes were reversed by sulfosuccinimidyl oleate (SSO; CD\u201036 inhibitor) treatment. Moreover, SCID mice bearing Lv.MTDH\u2010Wt\/\u03947\u2010MDA\u2010MB\u2010231cells\n                    <jats:sup>CAF\u2010TAM<\/jats:sup>\n                    heterotypic spheroids led to accelerated breast tumor growth and lipid\u2010driven metastasis. Importantly, SSO administration significantly reduced lipid accumulation and tumor aggressiveness, confirming CD36 as a functional mediator of MTDH\u2010driven lipid reprogramming. Our findings establish MTDH as a master regulator of lipid reprogramming through CD36, a process further amplified by CAF\u2010TAM interactions, which creates a lipid\u2010rich tumor microenvironment fuelling TNBC aggressiveness. This study reveals crucial mechanistic insights into how stromal\u2010immune cells induce lipid symbiosis and highlights the MTDH\u2010CD36 axis as a promising therapeutic target for future combination therapies in aggressive, metabolically reprogrammed TNBC.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202504890","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T06:14:46Z","timestamp":1769667286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metadherin with Stromal\u2010Immune Cues Drives CD36\u2010Dependent Lipid Reprogramming and Metastasis in Triple\u2010Negative Breast Cancer: Insights from a Hetero\u2010Spheroid Model"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0351-6324","authenticated-orcid":false,"given":"Soumyadeep","family":"Poddar","sequence":"first","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashikanta","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Shrivastava","sequence":"additional","affiliation":[{"name":"CSIR\u2010Centre for\u00a0Cellular and\u00a0Molecular Biology  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-7553","authenticated-orcid":false,"given":"Srigiridhar","family":"Kotamraju","sequence":"additional","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2606-7338","authenticated-orcid":false,"given":"Biswajit","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research  Ghaziabad India"},{"name":"School of Biosciences, Engineering and Technology Vellore Institute of Technology  Madhya Pradesh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12943\u2010025\u201002258\u20101"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2024.1424237\/XML\/NLM"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7150\/IJBS.92125"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMLET.2023.12.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES29020531"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS12121605"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS11223556"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2024.113947"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/CURRONCOL29110642"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/NATURE20791"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201012\u20100107"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/FCELL.2022.1079076"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13045\u2010023\u201001498\u20102"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/NU10060772"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/CANCERS14143449"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12943\u2010019\u20100980\u20108"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/D41586\u2010024\u201002868\u20107"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.7150\/IJBS.86039"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.11.008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/CBDD.14416"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/FEBS.16605"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41388\u2010019\u20101126\u20106"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/JBC.M115.661801"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS25179438"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aanat.2017.10.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/SREP11453"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1242\/BIO.2012653"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180765"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12951\u2010023\u201002021\u2010Y"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/CANCERS13235955"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/FONC.2022.881207"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/BJC.2013.768"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41420\u2010023\u201001306\u20103"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2021.799428"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175087"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201015\u20100930"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPHA.2023.115425"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/CBDD.14416"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3748\/WJG.V30.I20.2624"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.MCE.2017.01.031"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13045\u2010022\u201001349\u20106"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3892\/OR.2019.7206"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.09.013"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.07.030"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELLSIG.2024.111274"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/ACS.JPCB.8B07305\/ASSET\/IMAGES\/MEDIUM\/JP\u20102018\u201007305T_0007.GIF"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1242\/JCS.260419"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI.INSIGHT.141670"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.4161\/15384101.2014.949501"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TRSL.2023.11.006"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2021.119085"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2024.101661"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/S40164\u2010020\u201000191\u20101"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPET.2025.103529"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/S10555\u2010023\u201010156\u20105"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/NATURE02110"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3390\/MOLECULES25173935"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.11.010"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/S40364\u2010024\u201000645\u20102"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS10020472"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.1901176116\/\u2010\/DCSUPPLEMENTAL"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202504890","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.202504890","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202504890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T18:07:39Z","timestamp":1775844459000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202504890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":61,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/adhm.202504890"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202504890","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"assertion":[{"value":"2025-10-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e04890"}}