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

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

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

15 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)28826-28839
ページ数14
ジャーナルOncotarget
8
17
DOI
出版ステータス出版済み - 2017

ASJC Scopus 主題領域

  • 腫瘍学

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