The Embryonic Stem Cell-Specific Transcription Factor ZFP57 Promotes Liver Metastasis of Colorectal Cancer

• Published in: The Journal of surgical research Vol. 237; pp. 22 - 29
• Main Authors: Shoji, Yasuhiro, Takamura, Hiroyuki, Ninomiya, Itasu, Fushida, Sachio, Tada, Yuhki, Yokota, Takashi, Ohta, Tetsuo, Koide, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2019
• Subjects: Aged; Animals; Colon - pathology; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Female; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; IGF2; Liver - pathology; Liver metastasis; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - secondary; Lymphatic Metastasis - pathology; Male; Mice; Mice, Nude; Middle Aged; NANOG; Nanog Homeobox Protein - genetics; Nanog Homeobox Protein - metabolism; Progression-Free Survival; Rectum - pathology; Repressor Proteins - metabolism; Xenograft Model Antitumor Assays; ZFP57; IGF2; NANOG; ZFP57; Liver metastasis; Colorectal cancer
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2018.11.014

The embryonic stem cell-specific transcription factor, ZFP57, has been shown to play an important role in tumor formation. In this study, we examined if ZFP57 is involved in colorectal cancer metastasis. First, we used colorectal cancer cell lines to perform in vivo metastatic experiments with nude mice. Next, we carried out immunohistochemical analysis of clinical specimens of colorectal cancers. In liver metastatic experiments using human colorectal cancer HT29 and HCT116 cells, liver polymetastases occurred at high frequency in ZFP57-overexpressing HT29 and HCT116 cells, whereas both control cells only resulted in oligometastases. Next, we analyzed ZFP57 expression using clinical specimens. Liver metastasis-positive cases were more frequently associated with ZFP57 overexpression than negative cases in primary lesions of colorectal cancer, and the overexpression was particularly remarkable in tumor invasive lesions. Furthermore, ZFP57 overexpression was significantly correlated not only with liver metastasis but also with lymph node metastasis. In addition, the expression level of ZFP57 was significantly correlated with that of the metastasis-related gene NANOG. We also found that ZFP57 overexpression reduced the progression-free survival rate of patients with colorectal cancer. This study demonstrated that ZFP57 plays an important role in the hematogenous metastasis of colorectal cancer, suggesting that it could be used as a novel treatment target.