| RRC ID |
64356
|
| Author |
Huang R, Fujimura A, Nakata E, Takihira S, Inoue H, Yoshikawa S, Hiyama T, Ozaki T, Kamiya A.
|
| Title |
Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
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.
|
| Volume |
557
|
| Pages |
199-205
|
| Published |
2021-6-11
|
| DOI |
10.1016/j.bbrc.2021.03.172
|
| PII |
S0006-291X(21)00592-1
|
| PMID |
33872989
|
| MeSH |
Adaptor Proteins, Signal Transducing / metabolism
Cell Line, Tumor
Epinephrine / pharmacology*
Humans
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / metabolism*
Nerve Sheath Neoplasms / genetics
Nerve Sheath Neoplasms / metabolism*
Nerve Sheath Neoplasms / pathology
Prognosis
RNA Interference
Receptors, Adrenergic, beta-2 / genetics
Receptors, Adrenergic, beta-2 / metabolism*
Signal Transduction / drug effects*
Signal Transduction / genetics
Transcription Factors / metabolism
YAP-Signaling Proteins
|
| IF |
2.985
|
| Resource |
| Human and Animal Cells |
HS-PSS(RCB2362) |
