CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis

被引：33

作者：

Lai, Qiuhua ^{[1
]}

Li, Qingyuan ^{[1
]}

He, Chengcheng ^{[1
]}

Fang, Yuxin ^{[1
]}

Lin, Simin ^{[1
]}

Cai, Jianqun ^{[1
]}

Ding, Jian ^{[1
]}

Zhong, Qian ^{[1
]}

Zhang, Yue ^{[1
]}

Wu, Changjie ^{[1
]}

Wang, Xinke ^{[1
]}

He, Juan ^{[1
]}

Liu, Yongfeng ^{[1
]}

Yan, Qun ^{[1
]}

Li, Aimin ^{[1
]}

Liu, Side ^{[1
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Gastroenterol, Guangdong Prov Key Lab Gastroenterol, Guangzhou, Guangdong, Peoples R China

来源：

AGING-US | 2020年 / 12卷 / 16期

关键词：

colorectal cancer; CTCF; Hedgehog; P53; chemotherapy resistance; GENE-EXPRESSION; COLON-CANCER; PATHWAY; BINDING; SURVEILLANCE; INACTIVATION; BEVACIZUMAB; METASTASIS; CHROMATIN; THERAPY;

D O I：

10.18632/aging.103648

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

CTCF is overexpressed in several cancers and plays crucial roles in regulating aggressiveness, but little is known about whether CTCF drives colorectal cancer progression. Here, we identified a tumor-promoting role for CTCF in colorectal cancer. Our study demonstrated that CTCF was upregulated in colorectal cancer specimens compared with adjacent noncancerous colorectal tissues. The overexpression of CTCF promoted colorectal cancer cell proliferation and tumor growth, while the opposite effects were observed in CTCF knockdown cells. Increased GLI1, Shh, PTCH1, and PTCH2 levels were observed in CTCF-overexpressing cells using western blot analyses. CCK-8 and apoptosis assays revealed that 5-fluorouracil chemosensitivity was negatively associated with CTCF expression. Furthermore, we identified that P53 is a direct transcriptional target gene of CTCF in colorectal cancer. Western blot and nuclear extract assays showed that inhibition of P53 can counteract Hedgehog signaling pathway repression induced by CTCF knockdown. In conclusion, we uncovered a crucial role for CTCF regulation that possibly involves the P53-Hedgehog axis and highlighted the clinical utility of colorectal cancer-specific potential therapeutic target as disease progression or clinical response biomarkers.yy

引用

页码：16270 / 16293

页数：24

共 52 条

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