Wiley Acta Medica Okayama 1347-9032 115 3 2024 Role of catecholamine synthases in the maintenance of cancer stem-like cells in malignant peripheral nerve sheath tumors 871 882 EN Haruyoshi Katayama Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Rongsheng Huang Department of Trauma Orthopedics, The Second Hospital of Dalian Medical University Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuto Itano Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshiyuki Kunisada Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Nakata Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshifumi Ozaki Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that are derived from Schwann cell lineage around peripheral nerves. As in many other cancer types, cancer stem cells (CSCs) have been identified in MPNSTs, and they are considered the cause of treatment resistance, recurrence, and metastasis. As an element defining the cancer stemness of MPNSTs, we previously reported a molecular mechanism by which exogenous adrenaline activates a core cancer stemness factor, YAP/TAZ, through β2 adrenoceptor (ADRB2). In this study, we found that MPNST cells express catecholamine synthases and that these enzymes are essential for maintaining cancer stemness, such as the ability to self-renew and maintain an undifferentiated state. Through gene knockdown and inhibition of these enzymes, we confirmed that catecholamines are indeed synthesized in MPNST cells. The results confirmed that catecholamine synthase knockdown in MPNST cells reduces the activity of YAP/TAZ. These data suggest that a mechanism of YAP/TAZ activation by de novo synthesized adrenaline, as well as exogenous adrenaline, may exist in the maintenance of cancer stemness of MPNST cells. This mechanism not only helps to understand the pathology of MPNST, but could also contribute to the development of therapeutic strategies for MPNST. No potential conflict of interest relevant to this article was reported.