IMR Press / FBL / Volume 23 / Issue 7 / DOI: 10.2741/4648

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Review

LINE-1-encoded reverse Transcriptase as a target in cancer therapy

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1 Italian National Health Institute, Rome, Italy
2 Department of Experimental Medicine and Surgery, University of Rome, Tor Vergata, Rome, Italy
3 Institute of Translational Pharmacology, CNR National Research Council of Italy, Rome, Italy
Front. Biosci. (Landmark Ed) 2018, 23(7), 1360–1369; https://doi.org/10.2741/4648
Published: 1 March 2018
Abstract

LINE-1 elements account for about 17% of the human genome and harbour two open reading frames: ORF1, encoding a 40 kDa RNA-binding protein, and ORF2, coding for a 150 kDa protein with reverse transcriptase (RT) activity. LINE-1s are highly expressed in embryos and tumor cells while being virtually silent in differentiated tissues and, consistently, both ORF-1p and ORF-2p have been detected in human cancers. RT-encoding ORF2 is expressed early in pre-neoplastic lesions suggesting that RT expression may be a potential cause, rather than a consequence, of cancer onset. Experimental data emerging from in vitro and in vivo studies confirm this view. Preclinical work showed that RT inhibition reduces proliferation, promotes differentiation of cancer cells and antagonizes tumor progression in murine models. Moreover, a recent phase II trial on metastatic hormone-resistant prostate cancer patients has confirmed the anticancer efficacy of RT inhibitors. Together, these data indicate that LINE-1-encoded RT emerges as a potential therapeutic target for a large spectrum of cancers and RT inhibitors as effective tools in a novel anti-cancer, non–cytotoxic, differentiation therapy.

Keywords
LINE-1 Retrotransposon
Reverse Transcriptase
Reverse Transcriptase Inhibitors
Cancer
Differentiation Therapy
Epigenetics
Review
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