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TOMM20 as a potential therapeutic target of colorectal cancer

Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. T...

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Autores principales: Park, Sang-Hee, Lee, Ah-Reum, Choi, Keonwoo, Joung, Soyoung, Yoon, Jong-Bok, Kim, Sungjoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Biochemistry and Molecular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941759/
https://www.ncbi.nlm.nih.gov/pubmed/31818360
http://dx.doi.org/10.5483/BMBRep.2019.52.12.249
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author Park, Sang-Hee
Lee, Ah-Reum
Choi, Keonwoo
Joung, Soyoung
Yoon, Jong-Bok
Kim, Sungjoo
author_facet Park, Sang-Hee
Lee, Ah-Reum
Choi, Keonwoo
Joung, Soyoung
Yoon, Jong-Bok
Kim, Sungjoo
author_sort Park, Sang-Hee
collection PubMed
description Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20’s contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer.
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spelling pubmed-69417592020-01-08 TOMM20 as a potential therapeutic target of colorectal cancer Park, Sang-Hee Lee, Ah-Reum Choi, Keonwoo Joung, Soyoung Yoon, Jong-Bok Kim, Sungjoo BMB Rep Articles Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20’s contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer. Korean Society for Biochemistry and Molecular Biology 2019-12 2019-12-31 /pmc/articles/PMC6941759/ /pubmed/31818360 http://dx.doi.org/10.5483/BMBRep.2019.52.12.249 Text en Copyright © 2019 by the The Korean Society for Biochemistry and Molecular Biology This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Park, Sang-Hee
Lee, Ah-Reum
Choi, Keonwoo
Joung, Soyoung
Yoon, Jong-Bok
Kim, Sungjoo
TOMM20 as a potential therapeutic target of colorectal cancer
title TOMM20 as a potential therapeutic target of colorectal cancer
title_full TOMM20 as a potential therapeutic target of colorectal cancer
title_fullStr TOMM20 as a potential therapeutic target of colorectal cancer
title_full_unstemmed TOMM20 as a potential therapeutic target of colorectal cancer
title_short TOMM20 as a potential therapeutic target of colorectal cancer
title_sort tomm20 as a potential therapeutic target of colorectal cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941759/
https://www.ncbi.nlm.nih.gov/pubmed/31818360
http://dx.doi.org/10.5483/BMBRep.2019.52.12.249
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