Division of Neurobiology, Barrow Brain Tumor Research Center, Barrow Neurological Institute, Phoenix, AZ, 85013, USA.
Cell Mol Life Sci. 2018 Feb;75(3):385-402. doi: 10.1007/s00018-017-2608-8. Epub 2017 Aug 18.
Malignant gliomas are the most common, infiltrative, and lethal primary brain tumors affecting the adult population. The grim prognosis for this disease is due to a combination of the presence of highly invasive tumor cells that escape surgical resection and the presence of a population of therapy-resistant cancer stem cells found within these tumors. Several studies suggest that glioma cells have cleverly hijacked the normal developmental program of neural progenitor cells, including their transcriptional programs, to enhance gliomagenesis. In this review, we summarize the role of developmentally regulated signaling pathways that have been found to facilitate glioma growth and invasion. Furthermore, we discuss how the microenvironment and treatment-induced perturbations of these highly interconnected signaling networks can trigger a shift in cellular phenotype and tumor subtype.
恶性胶质瘤是最常见、浸润性和致命的原发性脑肿瘤,影响成年人群。这种疾病的预后严峻,是由于高度侵袭性肿瘤细胞的存在,这些细胞逃避手术切除,以及在这些肿瘤中发现的一群对治疗有抗性的癌症干细胞的存在。一些研究表明,神经胶质瘤细胞巧妙地劫持了神经祖细胞的正常发育程序,包括它们的转录程序,以增强神经胶质瘤的发生。在这篇综述中,我们总结了发育调控信号通路在促进神经胶质瘤生长和侵袭中的作用。此外,我们还讨论了微环境和治疗诱导的这些高度相互关联的信号网络的干扰如何引发细胞表型和肿瘤亚型的转变。