Open AccessUpregulation of glucocorticoid receptor‐mediated glucose transporter 4 in enzalutamide‐resistant prostate cancer
Author(s) -
Hoshi Seiji,
Meguro Satoru,
Imai Hitomi,
Matsuoka Yuta,
Yoshida Yuki,
Onagi Akihumi,
Tanji Ryo,
HondaTakinami Ruriko,
Matsuoka Kanako,
Koguchi Tomoyuki,
Hata Junya,
Sato Yuichi,
Akaihata Hidenori,
Kataoka Masao,
Ogawa Soichiro,
Kojima Yoshiyuki
Publication year - 2021
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14865
Subject(s) - enzalutamide , downregulation and upregulation , prostate cancer , androgen receptor , glut4 , glucocorticoid receptor , endocrinology , cancer research , glucose transporter , medicine , chemistry , glucocorticoid , biology , cancer , biochemistry , insulin , gene
Enzalutamide (Enz) is a second‐generation androgen receptor (AR) antagonist for castration‐resistant prostate cancer (CRPC) therapy, and it prolongs survival time in these patients. However, during Enz treatment, CRPC patients usually acquire resistance to Enz and often show cross‐resistance to other AR signaling inhibitors. Although glucocorticoid receptor (GR) is involved in this resistance, the role of GR has not yet been clarified. Here, we report that chronic Enz treatment induced GR‐mediated glucose transporter 4 (GLUT4) upregulation, and that upregulation was associated with resistance to Enz and other AR signaling inhibitors. Additionally, inhibition of GLUT4 suppressed cell proliferation in Enz‐resistant prostate cancer cells, which recovered from Enz resistance and cross‐resistance without changes in GR expression. Thus, a combination of Enz and a GLUT4 inhibitor could be useful in Enz‐resistant CRPC patients.