Kang, Sang Soo Han, Kyung-Seok Ku, Bo Mi Lee, Yeon Kyung Hong, Jinpyo Shin, Hye Young Almonte, Antoine G. Woo, Dong Ho Brat, Daniel J. Hwang, Eun Mi Yoo, Seung Hyun Chung, Chun Kee Park, Sung-Hye Paek, Sun Ha Roh, Eun Joo Lee, Sung Joong Park, Jae-Yong Traynelis, Stephen F. Lee, C. Justin 2024-01-20T20:00:55Z 2024-01-20T20:00:55Z 2021-09-02 2010-02-01 0008-5472 https://pubs.kist.re.kr/handle/201004/131727 Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including in deadly glioblastomas of the brain that aggressively invade neighboring tissue. We hypothesized that disturbing Ca2+ signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca2+ signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca2+ increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP(3)R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP(3)R3-mediated Ca2+ release, caffeine inhibited migration of glioblastoma cells in various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft model of glioblastoma. These findings suggest IP(3)R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma. Cancer Res; 70(3); 1173-83. (C)2010 AACR. English AMER ASSOC CANCER RESEARCH GROWTH-FACTOR RECEPTOR UVB-INDUCED APOPTOSIS SKH-1 MICE MIGRATION SIGNALS PLASMA COMMON BRAIN CELLS Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival Article 10.1158/0008-5472.CAN-09-2886 1 CANCER RESEARCH, v.70, no.3, pp.1173 - 1183 CANCER RESEARCH 70 3 1173 1183 scie scopus 000278485600035 2-s2.0-76249129621 Oncology Oncology Article GROWTH-FACTOR RECEPTOR UVB-INDUCED APOPTOSIS SKH-1 MICE MIGRATION SIGNALS PLASMA COMMON BRAIN CELLS