Syntenin-1 promotes colorectal cancer stem cell expansion and chemoresistance by regulating prostaglandin E2 receptor

Background The protein syntenin-1 is expressed by a variety of cell types, and is upregulated in various malignancies, including melanoma, breast cancer and glioma. Although the mechanism by which elevated syntenin-1 expression contributes to cancer has been described, the exact pathway has not been...

Full description

Saved in:
Bibliographic Details
Published in:British journal of cancer 2020-09, Vol.123 (6), p.955-964
Main Authors: Iwamoto, Kazuya, Takahashi, Hidekazu, Okuzaki, Daisuke, Osawa, Hideo, Ogino, Takayuki, Miyoshi, Norikatsu, Uemura, Mamoru, Matsuda, Chu, Yamamoto, Hirofumi, Mizushima, Tsunekazu, Mori, Masaki, Doki, Yuichiro, Eguchi, Hidetoshi
Format: Article
Language:English
Subjects:
631/250/256/2515
631/67/1504/1885
631/67/1857
631/67/71
Aged
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Celecoxib
Cell Line, Tumor
Cell Movement
Chemoresistance
Colorectal cancer
Colorectal carcinoma
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Cyclooxygenase-2
DNA microarrays
Drug Resistance
Drug Resistance, Neoplasm
Epidemiology
Female
Glioma
HEK293 Cells
Humans
Inflammation
Male
Melanoma
Middle Aged
Molecular Medicine
Neoplastic Stem Cells - pathology
Oncology
Oxaliplatin
Oxaliplatin - pharmacology
Phenotypes
Polymerase chain reaction
Prognosis
Prostaglandin E2
Receptors, Prostaglandin E - physiology
Stem cells
Syntenins - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background The protein syntenin-1 is expressed by a variety of cell types, and is upregulated in various malignancies, including melanoma, breast cancer and glioma. Although the mechanism by which elevated syntenin-1 expression contributes to cancer has been described, the exact pathway has not been elucidated. Methods To investigate the involvement of syntenin-1 in colorectal cancer (CRC), we performed immunohistochemical analysis of 139 CRC surgical specimens. We also examined syntenin-1 knockdown in CRC cell lines. Results High syntenin-1 expression was associated with less differentiated histologic grade and poor prognosis, and was an independent prognostic indicator in CRC. Syntenin-1 knockdown in CRC cells reduced the presence of cancer stem cells (CSCs), oxaliplatin chemoresistance and migration. DNA microarray analysis and quantitative real-time polymerase chain reaction showed decreased prostaglandin E2 receptor 2 (PTGER2) expression in syntenin-1-knockdown cells. PTGER2 knockdown in CRC cells yielded the same phenotype as syntenin-1 knockdown. Celecoxib, which has anti-inflammatory effects by targeting cyclooxygenase-2, reduced CSCs and decreased chemoresistance, while prostaglandin E2 (PGE2) had the opposite effect. Conclusions Our findings suggested that syntenin-1 enhanced CSC expansion, oxaliplatin chemoresistance and migration capability through regulation of PTGER2 expression. Syntenin-1 may be a promising new prognostic factor and target for anti-cancer therapies.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-020-0965-9