Detailed Information

Cited 18 time in webofscience Cited 20 time in scopus
Metadata Downloads

Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer

Authors
Park, Seong HyeJo, Min JeeKim, Bo RamJeong, Yoon A.Na, Yoo JinKim, Jung LimJeong, SoyeonYun, Hye KyeongKim, Dae YeongKim, Bu GyeomKang, Sang HeeOh, Sang CheulLee, Dae-Hee
Issue Date
2019
Publisher
Ivyspring International Publisher
Keywords
colorectal cancer; Cetuximab Resistance; EPHB3; GLI-1
Citation
Theranostics, v.9, no.8, pp.2235 - 2251
Indexed
SCIE
SCOPUS
Journal Title
Theranostics
Volume
9
Number
8
Start Page
2235
End Page
2251
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/2769
DOI
10.7150/thno.30678
ISSN
1838-7640
Abstract
A major problem of colorectal cancer (CRC) targeted therapies is relapse caused by drug resistance. In most cases of CRC, patients develop resistance to anticancer drugs. Cetuximab does not show many of the side effects of other anticancer drugs and improves the survival of patients with metastatic CRC. However, the molecular mechanism of cetuximab resistance is not fully understood. Methods: EPHB3-mediated cetuximab resistance was confirmed by in vitro western blotting, colony-forming assays, WST-1 colorimetric assay, and in vivo xenograft models (n = 7 per group). RNA-seq analysis and receptor tyrosine kinase assays were performed to identify the cetuximab resistance mechanism of EPHB3. All statistical tests were two-sided. Results: The expression of EFNB3, which upregulates the EPHB3 receptor, was shown to be increased via microarray analysis. When resistance to cetuximab was acquired, EPHB3 protein levels increased. Hedgehog signaling, cancer stemness, and epithelial-mesenchymal transition signaling proteins were also increased in the cetuximab-resistant human colon cancer cell line SW48R. Despite cells acquiring resistance to cetuximab, STAT3 was still responsive to EGF and cetuximab treatment. Moreover, inhibition of EPHB3 was associated with decreased STAT3 activity. Co-immunoprecipitation confirmed that EGFR and EPHB3 bind to each other and this binding increases upon resistance acquisition, suggesting that STAT3 is activated by the binding between EGFR and EPHB3. Protein levels of GLI-1, SOX2, and Vimentin, which are affected by STAT3, also increased. Similar results were obtained in samples from patients with CRC. Conclusion: EPHB3 expression is associated with anticancer drug resistance.
Files in This Item
There are no files associated with this item.
Appears in
Collections
3. Graduate School > Graduate School > 1. Journal Articles
2. Clinical Science > Department of Medical Oncology and Hematology > 1. Journal Articles
2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles
4. Research institute > Institute of Convergence New Drug Development > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Jo, Min Jee photo

Jo, Min Jee
연구소 (Institute of Convergence New Drug Development)
Read more

Altmetrics

Total Views & Downloads

BROWSE