Abstract：
Doublecortin (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.
摘要：
Doublecortin（DCX）阳性神经祖细胞样细胞据称是癌症微环境的组成部分。据报道，组织中DCX阳性细胞的数量与癌症进展有关；然而，对这些细胞影响癌症进展的机制知之甚少。在这里，我们证明了DCX阳性细胞，在肺癌的所有主要组织学亚型中都有发现，是癌症相关的雪旺氏细胞（CAS），并通过建立肾上腺素能的微环境促进肺癌细胞的化学抗性。机械上,Hippo换能器YAP/TAZ的激活参与了CAS和DCX阳性新性状的获得。我们进一步揭示了CAS表达儿茶酚胺合成酶并合成肾上腺素，通过激活YAP/TAZ增强肺癌细胞的化学抗性。我们的发现揭示了CAS，通过YAP/TAZ在肺癌组织中的相互调节来驱动肾上腺素能微环境的形成。
