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Title 

Co-delivery of LETM1 and CTMP synergistically inhibits tumor growth in H-ras12V liver cancer model mice

Authors 

J Y ShinY S ChungB KangH L JiangDae Yeul YuK HanC ChaeJ H MoonG JangM H Cho

Publisher 

Nature Publishing Group

Issue Date 

2013

Citation 

Cancer Gene Therapy, vol. 20, no. 3, pp. 186-194

Keywords 

2A-peptideCTMPGPCSLETM1liver cancer

Abstract 

As hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, development of novel therapeutic approaches for HCC is urgently needed. Two different genes, LETM1 and CTMP, which target mitochondrial functions, were chosen and linked using 2A-peptide sequence. Successful self-cleavage of 2A-peptide induced synergistic antitumor effect in the liver of H-ras12V, the HCC model mice, by simultaneous activation of LETM1 (Leucine zipperEF hand-containing transmembrane-1) and CTMP (carboxyl-terminal modulator protein). Overexpression of LETM1 and CTMP significantly reduced the incidence of tumorigenesis, which were confirmed by gross and microscopic observations. Morphological changes in mitochondria, such as swelling and loss of cristae, were significant, and the prolonged activation of defects in mitochondrial function led to mitochondria-mediated apoptosis. Furthermore, with CTMP as a direct binding partner of Akt1, and LETM1 as a binding partner of CTMP, LETM1-2A-CTMP downregulated the Akt1 pathway at both Ser473 and Thr308 sites of phosphorylation. Proliferation and angiogenesis, which are important in cancer prognosis, were reduced in tumor sites after introduction of LETM1-2A-CTMP. Taken together, the results indicate that introduction of the mitochondria-targeting genes, LETM1 and CTMP, and self-processing capacity of 2A-peptide sequence exerts an antitumor effect in liver of H-ras12V mice, suggesting its potential as a tool for gene therapy.

ISSN 

0929-1903

Link 

http://dx.doi.org/10.1038/cgt.2013.6

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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