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Drug Resistance Mediated by AEG-1/MTDH/LYRIC
Book chapter   Open access   Peer reviewed

Drug Resistance Mediated by AEG-1/MTDH/LYRIC

Xiangbing Meng, Kristina W Thiel and Kimberly K Leslie
Advances in Cancer Research, pp.135-157
Elsevier Science & Technology
2013
DOI: 10.1016/B978-0-12-401676-7.00005-X
PMCID: PMC3967868
PMID: 23889990
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3967868View
Open Access

Abstract

AEG-1/MTDH/LYRIC has been shown to promote cancer progression and development. Overexpression of AEG-1/MTDH/LYRIC correlates with angiogenesis, metastasis, and chemoresistance to various chemotherapy agents in cancer cells originating from a variety of tissues. In this chapter, we focus on the role of AEG-1/MTDH/LYRIC in drug resistance. Mechanistic studies have shown that AEG-1/MTDH/LYRIC is involved in classical oncogenic pathways including Ha-Ras, myc, NFκB, and PI3K/Akt. AEG-1/MTDH/LYRIC also promotes protective autophagy by activating AMP kinase and autophagy-related gene 5. Another reported mechanism by which AEG-1/MTDH/LYRIC regulates drug resistance is by increasing loading of multidrug resistance gene (MDR) 1 mRNA to the polysome, thereby facilitating MDR1 protein translation. More recently, a novel function for AEG-1/MTDH/LYRIC as an RNA-binding protein was elucidated, which has the potential to impact expression of drug sensitivity or resistance genes. Finally, AEG-1/MTDH/LYRIC acts in microRNA-directed gene silencing via an interaction with staphylococcal nuclease and tudor domain containing 1, a component of the RNA-induced silencing complex. Altered microRNA expression and activity induced by AEG-1/MTDH/LYRIC represent an additional way that AEG-1/MTDH/LYRIC may cause drug resistance in cancer. The multiple functions of AEG-1/MTDH/LYRIC in drug resistance highlight that it is a viable target as an anticancer agent for a wide variety of cancers.
NFκB miR-375 AEG-1/MTDH/LYRIC SND1 Chemoresistance

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