Journal
RADIOTHERAPY AND ONCOLOGY
Volume 124, Issue 3, Pages 395-402Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2017.03.002
Keywords
G9a; CD133; DNA damage response; Chemoradioresistance; Cancer stem cells; PP2A
Funding
- Ministry of Science and Technology of Republic of China [103-2314-B-037-075, 104-2314-B-037-004, 105-2314-B-037-001]
- Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan [KMU-TP104A12]
- Biosignature in Colorectal Cancers, Academia Sinica, Taiwan
Ask authors/readers for more resources
Background and purpose: Neoadjuvant concurrent chemoradiotherapy (CCRT) is a standard treatment of locally advanced colon cancer cell (CRC). In order to maximize efficacy and minimize toxicity, new drugs have been developed and used in combination with CCRT. Recently, it has been shown that G9a plays a role in mediating phenotypes of cancer stem cells (CSCs). This study aimed to characterize G9a as a biomarker in predicting therapy response to prevent overtreatment and adverse effects in CRC patients. Experimental design: The primary tumors from 39 patients who received CCRT for rectal cancer were selected. In vivo tumor xenograft models for tumorigenic properties in immunodeficient mice were developed. In vitro sternness ability was performed by tumor-sphere assays, cell response to anticancer agents and stemness-related genes analysis. Results: Cells survived from radiation treatment, and displayed high levels of G9a. A significantly positive correlation was shown between G9a and CSCs marker CD133 in locally advanced rectal cancer patients with CCRT. Knockdown of G9a increased the sensitivity of cells to radiation treatment and sensitized cells to DNA damage agents through PP2A-RPA axis. Conclusions: Our study theorized that G9a might serve as a novel target in colon cancer, which offers exciting potential in prediction of response to preoperative chemoradiotherapy in patients with advanced CRC. (C) 2017 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available