DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) of the Replication Factor Complex CTF18-RFC is Critical for Colon Cancer Cell Growth

Jong-Tae Kim^1*, Hee Jun Cho^1*, Sang Yoon Park¹, Byung Moo Oh^1,2, Yo Sep Hwang^1,2, Kyoung Eun Baek¹, Young-Ha Lee³, Hee Cheol Kim^4✉, Hee Gu Lee^1,2✉

1. Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.
2. Department of Biomolecular Science, University of Science and Technology (UST), Daejeon, Republic of Korea.
3. Department of Infection Biology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
^*These authors contributed equally to this work.

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Citation:
Kim JT, Cho HJ, Park SY, Oh BM, Hwang YS, Baek KE, Lee YH, Kim HC, Lee HG. DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) of the Replication Factor Complex CTF18-RFC is Critical for Colon Cancer Cell Growth. J Cancer 2019; 10(24):6142-6153. doi:10.7150/jca.32339. Available from http://www.jcancer.org/v10p6142.htm

Abstract

DNA replication and sister chromatid cohesion 1 (DSCC1) combines with chromosome transmission-fidelity protein 18 (CTF18) to form a CTF18-DSCC1-CTF8 (CTF18-1-8) module, which in combination with CTF18-replication factor C (RFC) acts as a proliferating cell nuclear antigen (PCNA) loader during DNA replication-associated processes. It was found that DSCC1 was overexpressed in tumor tissues from patients with colon cancer and that the survival probability of patients with colon cancer was lower when the expression of cytosolic DSCC1 was higher in tumor regions (P=0.047). By using DSCC1- or CTF18-knockdown cell lines (HCT116-shDSCC1 or HCT116-shCTF18, respectively), it was confirmed that DSCC1-knockdown inhibits cell proliferation and invasion, but that CTF18-knockdown does not. Tumors in mice xenografted with shDSCC1 cells were significantly smaller compared with those in mice in the mock group or those xenografted with shCTF18 cells. The shDSCC1 cells were highly sensitive to γ-irradiation and other DNA replication inhibitory treatments, resulting in low cell viability. The present results suggested that DSCC1 is the most important component in the CTF18-1-8 module for CTF18-RFC and is highly relevant to the growth and metastasis of colon cancer cells, and, therefore, it may be a potential therapeutic target for colon cancer treatment.

Keywords: DSCC1, CTF18, CTF18-1-8 module, colon cancer, metastasis