Adrenergic microenvironment driven by cancer‐associated Schwann cells contributes to chemoresistance in patients with lung cancer

Abstract

AbstractDoublecortin (DCX)‐positive neural progenitor‐like cells are purported components of the cancer microenvironment. The number of DCX‐positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX‐positive cells, which are found in all major histological subtypes of lung cancer, are cancer‐associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine‐synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.