J Cancer 2021; 12(18):5385-5393. doi:10.7150/jca.57463
Mutation SVCT2 promotes cell proliferation, invasion and migration in colorectal cancer
1. Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea
2. Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
3. Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
* These authors contributed equally to this work.
Park SS, Ryu YS, Koh DI, Hong SW, Moon JH, Shin JS, Kim MJ, Kim DY, Hong JK, Kim EH, Jeong HR, Park YS, Kim J, Kim DM, Yun H, Shin JY, Jin DH. Mutation SVCT2 promotes cell proliferation, invasion and migration in colorectal cancer. J Cancer 2021; 12(18):5385-5393. doi:10.7150/jca.57463. Available from https://www.jcancer.org/v12p5385.htm
The sodium-dependent vitamin C transporter 2 (SVCT2) surface glycoprotein regulates ascorbate accumulation in the plasma, often resulting in the induction of cancer cell death. Therefore, high expression of this gene associates with increased overall survival in several cancers. However, in colorectal cancer (CRC), high (likely mutated) SVCT2 expression relates to poor overall survival, and its functional significance has not been studied. Thus, we hypothesize that mutant SVCT2 expression could affect CRC patient survival. According to biological databases, SVCT2 has been found to be mutated frequently, and SVCT2 E264K has a particularly high pathogenic score (0.98), compared to other SVCT2 mutant sites, in CRC patients. Interestingly, our results reveal expression of SVCT2 E264K in many CRC tissues and cells. Also, we found wild-type SVCT2 expression to be largely localized to the cytoplasm and membrane, while SVCT2 E264K was restricted to the cytoplasm. We further found that SVCT2 E264K overexpression increases cell growth. By contrast, SVCT2 E264K knockdown significantly reduced cell proliferation and promoted cell apoptosis, resulting in inhibition of cell invasion and migration. Taken together, SVCT2 E264K plays a critical role in proliferation in CRC. Our results suggest that SVCT2 E264K could be a promising novel therapeutic target in CRC.
Keywords: SVCT2, colorectal cancer, cell proliferation, invasion, migration