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

Author:

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 DevanandORCID,Wang Xiang-Yang,Das Swadesh K.,Emdad Luni,Fisher Paul B.

Abstract

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.

Funder

Virginia Catalyst

National Foundation for Cancer Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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