Behrooz Amir Barzegar, Syahir Amir
Department of Biochemistry, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia, Serdang, Malaysia.
MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia.
Front Oncol. 2021 Apr 1;11:642719. doi: 10.3389/fonc.2021.642719. eCollection 2021.
Glioblastoma multiforme (GBM) is one of the most lethal forms of primary brain tumors. Glioblastoma stem cells (GSCs) play an undeniable role in tumor development by activating multiple signaling pathways such as Wnt/β-catenin and PI3K/AKT/mTOR that facilitate brain tumor formation. CD133, a transmembrane glycoprotein, has been used to classify cancer stem cells (CSCs) in GBM. The therapeutic value of CD133 is a biomarker of the CSC in multiple cancers. It also leads to growth and recurrence of the tumor. More recent findings have confirmed the association of telomerase/TERT with Wnt/β-catenin and the PI3K/AKT/mTOR signaling pathways. Advance studies have shown that crosstalk between CD133, Wnt/β-catenin, and telomerase/TERT can facilitate GBM stemness and lead to therapeutic resistance. Mechanistic insight into signaling mechanisms downstream of surface biomarkers has been revolutionized by facilitating targeting of tumor-specific molecular deregulation. This review also addresses the importance of interplay between CD133, Wnt/β-catenin and TERT signaling pathways in GSCs and outlines the future therapeutic goals for glioblastoma treatment.
多形性胶质母细胞瘤（GBM）是最致命的原发性脑肿瘤之一。胶质母细胞瘤干细胞（GSCs）通过激活多种信号通路（如Wnt/β-连环蛋白和PI3K/AKT/mTOR）在肿瘤发展中发挥不可否认的作用，这些信号通路促进脑肿瘤形成。CD133是一种跨膜糖蛋白，已被用于对GBM中的癌症干细胞（CSCs）进行分类。CD133作为CSC的生物标志物在多种癌症中具有治疗价值。它还会导致肿瘤的生长和复发。最近的研究结果证实了端粒酶/TERT与Wnt/β-连环蛋白以及PI3K/AKT/mTOR信号通路之间的关联。前期研究表明，CD133、Wnt/β-连环蛋白和端粒酶/TERT之间的相互作用可促进GBM的干性并导致治疗耐药性。通过促进对肿瘤特异性分子失调的靶向作用，对表面生物标志物下游信号机制的深入了解带来了变革。本综述还阐述了CD133、Wnt/β-连环蛋白和TERT信号通路在GSCs中相互作用的重要性，并概述了胶质母细胞瘤治疗的未来治疗目标。
