DNA Replication and Sister Chromatid Cohesion 1 (DSCC1) of the Replication Factor Complex CTF18-RFC is Critical for Colon Cancer Cell Growth
| Autor: | Yo Sep Hwang, Young-Ha Lee, Jong-Tae Kim, Kyoung Eun Baek, Hee Gu Lee, Byung Moo Oh, Hee Cheol Kim, Hee Jun Cho, Sang Yoon Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Colorectal cancer Cell growth DNA replication DSCC1 Biology medicine.disease Metastasis Proliferating cell nuclear antigen Establishment of sister chromatid cohesion 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology colon cancer Cell culture 030220 oncology & carcinogenesis CTF18 medicine Cancer research biology.protein metastasis Viability assay CTF18-1-8 module Research Paper |
| Zdroj: | Journal of Cancer |
| ISSN: | 1837-9664 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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