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

Abstract

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.

• Authors: Kazuya Iwamoto, Hidekazu Takahashi, Daisuke Okuzaki, Hideo Osawa, Takayuki Ogino, Norikatsu Miyoshi, Mamoru Uemura, Chu Matsuda, Hirofumi Yamamoto, Tsunekazu Mizushima, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi
• Journal: British journal of cancer (Br J Cancer) Vol. 123 Issue 6 Pg. 955-964 (09 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 32595209 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Prostaglandin E
• Syntenins
• Oxaliplatin

Topics

• Aged
• Cell Line, Tumor
• Cell Movement
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Drug Resistance, Neoplasm
• Female
• HEK293 Cells
• Humans
• Male
• Middle Aged
• Neoplastic Stem Cells (pathology)
• Oxaliplatin (pharmacology)
• Prognosis
• Receptors, Prostaglandin E (physiology)
• Syntenins (physiology)