AUTHOR=Zhang Qing , Yang Lianhe , Guan Gefei , Cheng Peng , Cheng Wen , Wu Anhua TITLE=LOXL2 Upregulation in Gliomas Drives Tumorigenicity by Activating Autophagy to Promote TMZ Resistance and Trigger EMT JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.569584 DOI=10.3389/fonc.2020.569584 ISSN=2234-943X ABSTRACT=

Glioma is the most prevalent primary brain tumor in adults and has an extremely unfavorable prognosis. As a member of the lysyl oxidase (LOX) family, lysyl-oxidase-like-2 (LOXL2) is known to play different roles in different tumors. However, the role of LOXL2 in glioma has not yet been fully elucidated. In the present study, we detected that LOXL2 was considerably upregulated in glioma and that LOXL2 upregulation was evidently related to glioma WHO grade, malignant molecular subtypes, and poor prognosis in glioma patients. Additionally, we found that LOXL2 not only promoted glioma cells proliferation, migration, invasion, and induced the epithelial-to-mesenchymal transition (EMT) process, but also reduced the sensitivity of glioma cells to temozolomide (TMZ). Furthermore, we identified that LOXL2 reduced TMZ sensitivity and induced EMT in glioma via the activation of autophagy. Mechanistically, LOXL2 enhanced Atg7 expression by promoting the phosphorylation of Erk1/2, leading to the activation of autophagy and regulation of EMT process and TMZ sensitivity through autophagy. Our study describes an LOXL2-Erk1/2-Atg7 signaling axis that influences glioma EMT and chemosensitivity through autophagy; moreover, LOXL2 may serve as a promising therapeutic target in the treatment of glioma.