Biomol Ther.  2018 May;26(3):313-321. 10.4062/biomolther.2017.033.

Cellular Prion Protein Enhances Drug Resistance of Colorectal Cancer Cells via Regulation of a Survival Signal Pathway

• Lee JH
• Yun CW
• Lee SH

• KMID: 2421741
• DOI: http://doi.org/10.4062/biomolther.2017.033

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.

Keyword

Colorectal cancer; Prion protein; Drug resistance; 5-fluorouracil; Anticancer

MeSH Terms

Apoptosis
Caspase 3
Cell Survival
Colorectal Neoplasms*
Cyclin D1
Cyclin E
Cyclins
Drug Resistance*
Drug Therapy
Fluorouracil
Signal Transduction*
Caspase 3
Cyclin D1
Cyclin E
Cyclins
Fluorouracil