AGR2 is a target of canonical Wnt/β-catenin signaling and is important for stemness maintenance in colorectal cancer stem cells
| Autor: | Yun Hak Kim, Ji Hye Park, Jong Seong Ha, Songhwa Kang, Shreekrishna Lamichane, Yeon-Ju Kim, Da Yeon Kim, Li Dehua, Seung Taek Ji, Sang-Mo Kwon, Seok Yun Jung, Jisoo Yun, Woong Bi Jang, Babita Dahal Lamichane |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Colorectal cancer Biophysics AGR2 Biology Stem cell marker Biochemistry Metastasis 03 medical and health sciences Mucoproteins 0302 clinical medicine Cancer stem cell Cell Line Tumor Spheroids Cellular medicine Humans Gene Silencing Neoplasm Metastasis Wnt Signaling Pathway Molecular Biology beta Catenin Oncogene Proteins Oncogene Gene Expression Profiling Wnt signaling pathway Cell Biology HCT116 Cells medicine.disease Gene Expression Regulation Neoplastic Wnt Proteins HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Stem cell Colorectal Neoplasms Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 515:600-606 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2019.05.154 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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