LOXL1 confers antiapoptosis and promotes gliomagenesis through stabilizing BAG2

Abstract

The lysyl oxidase (LOX) family is closely related to the progression of glioma. To ensure the clinical significance of LOX family in glioma, The Cancer Genome Atlas (TCGA) database was mined and the analysis indicated that higher LOXL1 expression was correlated with more malignant glioma progression. The functions of LOXL1 in promoting glioma cell survival and inhibiting apoptosis were studied by gain- and loss-of-function experiments in cells and animals. LOXL1 was found to exhibit antiapoptotic activity by interacting with multiple antiapoptosis modulators, especially BAG family molecular chaperone regulator 2 (BAG2). LOXL1-D515 interacted with BAG2-K186 through a hydrogen bond, and its lysyl oxidase activity prevented BAG2 degradation by competing with K186 ubiquitylation. Then, we discovered that LOXL1 expression was specifically upregulated through the VEGFR-Src-CEBPA axis. Clinically, the patients with higher LOXL1 levels in their blood had much more abundant BAG2 protein levels in glioma tissues. Conclusively, LOXL1 functions as an important mediator that increases the antiapoptotic capacity of tumor cells, and approaches targeting LOXL1 represent a potential strategy for treating glioma. In addition, blood LOXL1 levels can be used as a biomarker to monitor glioma progression.

Longitudinal single-cell transcriptomics reveals distinct patterns of recurrence in acute myeloid leukemia

“…As expected, these CNVs caused differential gene expression at these loci (Fig. 2D), such as LOXL1 and FAM81A implicated in cancer progression [24].…”

“…6F). The Re trajectory (cluster 5 towards cluster 9) is hallmarked by upregulation of numerous genes required for differentiation, leukemia progression and chemo-resistance, including RACK1 [45], EREG [46] and LOXL1 [24] (Fig. 6F).…”

DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing

“…Carbamidomethyl (C) was set as the fixed modification, and oxidation (M) and acetylation (Protein N-term) were added as variable modifications. iBAQ values calculated by MaxQuant software were used for protein quantitation according to a previous study (Yu et al, 2020). Proteins identified in two of the three biological replicates (fold-change higher than 2 or identified only in the HA-DRAK2 group) were defined as potential candidates and used for further bioinformatics analysis.…”

Roles of Lysyl Oxidase Family Members in the Tumor Microenvironment and Progression of Liver Cancer

“…Several lines of study have highlighted the role of LOXL1 in tumor progression, such as glioma [ 33 ], gastric cancer [ 34 ], colorectal cancer [ 35 ], pancreatic ductal adenocarcinoma (PDAC) [ 36 ], yet its effect on liver cancer remains unclear. The biological role of LOXL1 in eye disorders, particularly pseudoexfoliation syndrome and glaucoma, has been recently reviewed in detail by Greene et al [ 37 ].…”