TY - JOUR
T1 - Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors
AU - Huang, Rongsheng
AU - Fujimura, Atsushi
AU - Nakata, Eiji
AU - Takihira, Shota
AU - Inoue, Hirofumi
AU - Yoshikawa, Soichiro
AU - Hiyama, Takeshi
AU - Ozaki, Toshifumi
AU - Kamiya, Atsunori
N1 - Funding Information:
This work was supported by the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Sciences, and Technology of Japan (grant number 20K07618 ) and the Japan Agency for Medical Research and Development (AMED) (grant numbers 18072932 and 20318557 ) and the Naito Foundation (2017) .
Publisher Copyright:
© 2021 The Authors
PY - 2021/6/11
Y1 - 2021/6/11
N2 - Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients’ specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.
AB - Malignant peripheral nerve sheath tumor (MPNST), a highly malignant tumor that arises in peripheral nerve tissues, is known to be highly resistant to radiation and chemotherapy. Although there are several reports on genetic mutations and epigenetic changes that define the pathogenesis of MPNST, there is insufficient information regarding the microenvironment that contributes to the malignancy of MPNST. In the present study, we demonstrate that adrenaline increases the cancer stem cell population in MPNST. This effect is mediated by adrenaline stimulation of beta-2 adrenergic receptor (ADRB2), which activates the Hippo transducer, YAP/TAZ. Inhibition and RNAi experiments revealed that inhibition of ADRB2 attenuated the adrenaline-triggered activity of YAP/TAZ and subsequently attenuated MPNST cells stemness. Furthermore, ADRB2-YAP/TAZ axis was confirmed in the MPNST patients’ specimens. The prognosis of patients with high levels of ADRB2 was found to be significantly worse. These data show that adrenaline exacerbates MPNST prognosis and may aid the development of new treatment strategies for MPNST.
KW - ADRB2
KW - Cancer stem-like cells
KW - MPNST
KW - YAP/TAZ
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U2 - 10.1016/j.bbrc.2021.03.172
DO - 10.1016/j.bbrc.2021.03.172
M3 - Article
C2 - 33872989
AN - SCOPUS:85104574288
SN - 0006-291X
VL - 557
SP - 199
EP - 205
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -
