Insights into the Mechanisms of Action of MDA-7/IL-24: A Ubiquitous Cancer-Suppressing Protein

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 tu...

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Published in:International journal of molecular sciences 2021-12, Vol.23 (1), p.72
Main Authors: Modi, Jinkal, Roy, Abhishek, Pradhan, Anjan K, Kumar, Amit, Talukdar, Sarmistha, Bhoopathi, Praveen, Maji, Santanu, Mannangatti, Padmanabhan, Sanchez De La Rosa, Daniel, Li, Jiong, Guo, Chunqing, Subler, Mark A, Windle, Jolene J, Cavenee, Webster K, Sarkar, Devanand, Wang, Xiang-Yang, Das, Swadesh K, Emdad, Luni, Fisher, Paul B
Format: Article
Language:English
Subjects:
Adenoviruses
Amino acids
Angiogenesis
Animal models
Animals
Antitumor activity
Apoptosis
Apoptosis - physiology
Autophagy
Autophagy - physiology
Biocompatibility
bystander antitumor activity
Cancer
Cell death
Cell Death - physiology
Cell differentiation
Cell division
Chemical bonds
Clinical trials
Cloning
combinatorial therapy
cytokine
Cytokines
Epigenetics
Gene expression
Humans
Interleukin 10
Interleukin 24
Interleukins - metabolism
Kinases
Mda-7 protein
MDA-7/IL-24
Melanoma
Melanoma - metabolism
Metastases
Metastasis
MicroRNAs
Protein expression
Proteins
Review
Tumor suppressor genes
Tumor Suppressor Proteins - metabolism
Tumors
Wound healing
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Summary: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 "bystander" 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23010072