RRC ID 64356
著者 Huang R, Fujimura A, Nakata E, Takihira S, Inoue H, Yoshikawa S, Hiyama T, Ozaki T, Kamiya A.
タイトル Adrenergic signaling promotes the expansion of cancer stem-like cells of malignant peripheral nerve sheath tumors.
ジャーナル 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.
巻・号 557
ページ 199-205
公開日 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
リソース情報
ヒト・動物細胞 HS-PSS(RCB2362)