TY - JOUR
T1 - GRIK2 has a role in the maintenance of urothelial carcinoma stem-like cells, and its expression is associated with poorer prognosis
AU - Inoue, Ryuta
AU - Hirohashi, Yoshihiko
AU - Kitamura, Hiroshi
AU - Nishida, Sachiyo
AU - Murai, Aiko
AU - Takaya, Akari
AU - Yamamoto, Eri
AU - Matsuki, Masahiro
AU - Tanaka, Toshiaki
AU - Kubo, Terufumi
AU - Nakatsugawa, Munehide
AU - Kanaseki, Takayuki
AU - Tsukahara, Tomohide
AU - Sato, Noriyuki
AU - Masumori, Naoya
AU - Torigoe, Toshihiko
N1 - Funding Information:
This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to N.S.), program for developing the supporting system for upgrading education and research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to N.S.), Health and Labor Sciences Research Grants, a grant-in-aid of Ono Cancer Research Fund (to T.T.), Suharakinenzaidan Co., Ltd. (to Y.H.), Grants-in-Aid for Regional R&D Proposal-Based Program from Northern Advancement Center for Science & Technology of Hokkaido Japan (to Y.H. and T.T.) and the project for development of innovative research on cancer therapeutics from Japan Agency for Medical Research and development, AMED.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - ALDH1
KW - Cancer stem-like cells
KW - GRIK2
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85018405915&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.16259
DO - 10.18632/oncotarget.16259
M3 - 学術論文
C2 - 28418868
AN - SCOPUS:85018405915
SN - 1949-2553
VL - 8
SP - 28826
EP - 28839
JO - Oncotarget
JF - Oncotarget
IS - 17
ER -