Research Paper Volume 12, Issue 16 pp 16270—16293
CTCF promotes colorectal cancer cell proliferation and chemotherapy resistance to 5-FU via the P53-Hedgehog axis
- 1 Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Received: March 7, 2020 Accepted: June 19, 2020 Published: July 20, 2020https://doi.org/10.18632/aging.103648
How to Cite
Copyright © 2020 Lai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.