Cellular Prion Protein Enhances Drug Resistance of Colorectal Cancer Cells via Regulation of a Survival Signal Pathway
- Authors
- Lee, Jun Hee; Yun, Chul Won; Lee, Sang Hun
- Issue Date
- May-2018
- Publisher
- 한국응용약물학회
- Keywords
- Colorectal cancer; Prion protein; Drug resistance; 5-fluorouracil; Anticancer
- Citation
- Biomolecules & Therapeutics, v.26, no.3, pp 313 - 321
- Pages
- 9
- Journal Title
- Biomolecules & Therapeutics
- Volume
- 26
- Number
- 3
- Start Page
- 313
- End Page
- 321
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/6027
- DOI
- 10.4062/biomolther.2017.033
- ISSN
- 1976-9148
2005-4483
- Abstract
- Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein (PrPC) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, PrPC expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, PrPC increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, PrPC inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of PrPC triggered apoptosis via the activation of caspase-3. These results indicate that PrPC plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with PrPC targeting may yield efficacious treatments of colorectal cancer.
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Collections - College of Medicine > Department of Biochemistry > 1. Journal Articles
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