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TOMM20 is a Potential Therapeutic Target of Colorectal Cancer
Sang-Hee Park1,2, Ah-Reum Lee1,2, Keonwoo Choi1,2, Soyoung Joung1,2, Jong-Bok Yoon3, SungJoo Kim2,*
1Biomedicine & Health Sciences and 2Medical Life Sciences, The Catholic University of Korea,
3Biochemistry, Yonsei University
Abstract
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 aim of this study is 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 affected 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 found to be overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including 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 a promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer.
Abstract, Accepted Manuscript(in press) [Submitted on October 15, 2019, Accepted on November 21, 2019]
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