GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis.

Abstract

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are small sub-population of cancer cells that are endowed with higher tumor-initiating ability, self-renewal ability and differentiation ability. CSCs/CICs could be isolated as high aldehyde dehydrogenase 1 activity cells (ALDH1high) from various cancer samples. In this study, we isolated urothelial carcinoma CSCs/CICs as ALDHhigh cells and investigated the molecular aspects. ALDH1high cells showed greater sphere-forming ability and higher tumor-initiating ability in immune-deficient mice than those of ALDH1low cells, indicating that CSCs/CICs were enriched in ALDH1high cells. cDNA microarray analysis revealed that an ionotropic glutamate receptor glutamate receptor, ionotropic, kainate 2 (GRIK2) was expressed in ALDH1high cells at a higher level than that in ALDH1low cells. GRIK2 gene knockdown by siRNAs decreased the sphere-forming ability and invasion ability, whereas GRIK2 overexpression increased the sphere-forming ability, invasion ability and tumorigenicity, indicating that GRIK2 has a role in the maintenance of CSCs/CICs. Immunohistochemical staining revealed that higher levels of GRIK2 and ALDH1 expression were related to poorer prognosis in urinary tract carcinoma cases. The findings indicate that GRIK2 has a role in the maintenance of urothelial CSCs/CICs and that GRIK2 and ALDH1 can be prognosis prediction markers for urinary tract carcinomas.

• Authors: Ryuta Inoue, Yoshihiko Hirohashi, Hiroshi Kitamura, Sachiyo Nishida, Aiko Murai, Akari Takaya, Eri Yamamoto, Masahiro Matsuki, Toshiaki Tanaka, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Noriyuki Sato, Naoya Masumori, Toshihiko Torigoe
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 17 Pg. 28826-28839 (Apr 25 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28418868 (Publication Type: Journal Article)

Chemical References

• Gluk2 kainate receptor
• Isoenzymes
• RNA, Small Interfering
• Receptors, Kainic Acid
• Aldehyde Dehydrogenase 1 Family
• ALDH1A1 protein, human
• ALDH1A1 protein, mouse
• Retinal Dehydrogenase

Topics

• Aldehyde Dehydrogenase 1 Family
• Animals
• Carcinogenesis
• Cell Line, Tumor
• Cell Self Renewal (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Isoenzymes (metabolism)
• Mice
• Mice, SCID
• Neoplastic Stem Cells (metabolism, pathology)
• Prognosis
• RNA, Small Interfering (genetics)
• Receptors, Kainic Acid (genetics, metabolism)
• Retinal Dehydrogenase (metabolism)
• Urologic Neoplasms (diagnosis, genetics, pathology)
• Urothelium (pathology)
• Xenograft Model Antitumor Assays