Retrotransposon-Encoded Reverse Transcriptase in the Genesis, Progression and Cellular Plasticity of Human Cancer

Cancers

Paola Sinibaldi-Vallebona¹  Claudia Matteucci¹ 

[1] Department of Experimental Medicine and Biochemical Sciences, University ‘Tor Vergata’, Rome, Italy; E-Mails:

关键词: tumorigenesis;    endogenous reverse transcriptase;    reverse transcriptase inhibitors;    early embryonic development;   

DOI  :  10.3390/cancers3011141

来源: mdpi

【 摘 要 】

LINE-1 (Long Interspersed Nuclear Elements) and HERVs (Human Endogenous Retroviruses) are two families of autonomously replicating retrotransposons that together account for about 28% of the human genome. Genes harbored within LINE-1 and HERV retrotransposons, particularly those encoding the reverse transcriptase (RT) enzyme, are generally expressed at low levels in differentiated cells, but their expression is upregulated in transformed cells and embryonic tissues. Here we discuss a recently discovered RT-dependent mechanism that operates in tumorigenesis and reversibly modulates phenotypic and functional variations associated with tumor progression. Downregulation of active LINE-1 elements drastically reduces the tumorigenic potential of cancer cells, paralleled by reduced proliferation and increased differentiation. Pharmacological RT inhibitors (e.g., nevirapine and efavirenz) exert similar effects on tumorigenic cell lines, both in culture and in animal models. The HERV-K family play a distinct complementary role in stress-dependent transition of melanoma cells from an adherent, non-aggressive, to a non-adherent, highly malignant, growth phenotype. In synthesis, the retrotransposon-encoded RT is increasingly emerging as a key regulator of tumor progression and a promising target in a novel anti-cancer therapy.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.