Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2019 Aug 6;515(4):600-606. doi: 10.1016/j.bbrc.2019.05.154. Epub 2019 Jun 6.

AGR2 is a target of canonical Wnt/β-catenin signaling and is important for stemness maintenance in colorectal cancer stem cells.

Author information

1
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea; Convergence Stem Cell Research Center, Pusan National University, Yangsan, Republic of Korea.
2
Convergence Stem Cell Research Center, Pusan National University, Yangsan, Republic of Korea; Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
3
Department of Anatomy and Department of Biomedical Informatics, School of Medicine, Pusan National University, Yangsan, Republic of Korea. Electronic address: yunhak10510@pusan.ac.kr.
4
Laboratory for Vascular Medicine and Stem Cell Biology, Medical Research Institute, Department of Physiology, School of Medicine, Pusan National University, Yangsan, 50612, Republic of Korea; Convergence Stem Cell Research Center, Pusan National University, Yangsan, Republic of Korea; Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea. Electronic address: smkwon323@pusan.ac.kr.

Abstract

Colorectal cancer is one of the leading causes of cancer-related deaths. Due to relapse after current therapy regimens, cancer stem cells (CSCs) are being studied to target this small tumor-initiating population. Anterior gradient 2 (AGR2), a disulfide isomerase protein, is a well-known pro-oncogenic/metastatic oncogene overexpressed in various tumor tissues, including colon cancer. We found that AGR2 was a novel stem cell marker that was regulated by the canonical Wnt/β-catenin pathway in colon CSCs. AGR2 was highly co-expressed with surface stem cell markers in spheroidal culture. Silencing of AGR2 resulted in decreased sphere-forming ability and down-regulated expression of stem cell markers, whereas the opposite effects were seen with AGR2 overexpression. Moreover, patients with high β-catenin and AGR2 expression showed lower overall survival than those with low expression. In conclusion, our study describes a novel role for AGR2 as a stem cell marker that is highly regulated by canonical Wnt/β-catenin signaling in colorectal cancer.

KEYWORDS:

AGR2; Cancer stem cell; Colorectal cancer; Metastasis; Wnt

PMID:
31178140
DOI:
10.1016/j.bbrc.2019.05.154

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center