{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:08:35Z","timestamp":1784268515944,"version":"3.55.0"},"reference-count":158,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Virginia Catalyst","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"InterLeukin Combinatorial Therapies, Inc.","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100001767","name":"National Foundation for Cancer Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100001767","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH\/NCI","award":["R01 CA244993"],"award-info":[{"award-number":["R01 CA244993"]}]},{"name":"NIH\/NCI","award":["R01 CA259599"],"award-info":[{"award-number":["R01 CA259599"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Melanoma differentiation associated gene-7\/interleukin-24 (MDA-7\/IL-24), a secreted protein of the IL-10 family, was first identified more than two decades ago as a novel gene differentially expressed in terminally differentiating human metastatic melanoma cells. MDA-7\/IL-24 functions as a potent tumor suppressor exerting a diverse array of functions including the inhibition of tumor growth, invasion, angiogenesis, and metastasis, and induction of potent \u201cbystander\u201d antitumor activity and synergy with conventional cancer therapeutics. MDA-7\/IL-24 induces cancer-specific cell death through apoptosis or toxic autophagy, which was initially established in vitro and in preclinical animal models in vivo and later in a Phase I clinical trial in patients with advanced cancers. This review summarizes the history and our current understanding of the molecular\/biological mechanisms of MDA-7\/IL-24 action rendering it a potent cancer suppressor.<\/jats:p>","DOI":"10.3390\/ijms23010072","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"72","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Insights into the Mechanisms of Action of MDA-7\/IL-24: A Ubiquitous Cancer-Suppressing Protein"],"prefix":"10.3390","volume":"23","author":[{"given":"Jinkal","family":"Modi","sequence":"first","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjan K.","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarmistha","family":"Talukdar","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Bhoopathi","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santanu","family":"Maji","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmanabhan","family":"Mannangatti","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Sanchez De La Rosa","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Subler","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolene J.","family":"Windle","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Webster K.","family":"Cavenee","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0973-2323","authenticated-orcid":false,"given":"Devanand","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swadesh K.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luni","family":"Emdad","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23218, USA"},{"name":"VCU Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, VA 23218, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Use of a Sensitive and Efficient Subtraction Hybridization Protocol for the Identification of Genes Differentially Regulated during the Induction of Differentiation in Human Melanoma Cells","volume":"1","author":"Jiang","year":"1993","journal-title":"Mol. 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