LOXL3 Silencing Affected Cell Adhesion and Invasion in U87MG Glioma Cells

International Journal of Molecular Sciences

Talita de S. Laurentino¹  Sueli M. Oba-Shinjo¹  Suely K. N. Marie¹  Roseli da S. Soares¹  Antonio M. Lerario² 

[1] Cellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-000, SP, Brazil;Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI 48109, USA;

关键词: LOXL3;    lysyl oxidase;    glioblastoma;    cytoskeleton;    extracellular matrix;    cell death;   

DOI  :  10.3390/ijms22158072

来源: DOAJ

【 摘 要 】

Lysyl oxidase-like 3 (LOXL3), belonging to the lysyl oxidase family, is responsible for the crosslinking in collagen or elastin. The cellular localization of LOXL3 is in the extracellular space by reason of its canonical function. In tumors, the presence of LOXL3 has been associated with genomic stability, cell proliferation, and metastasis. In silico analysis has shown that glioblastoma was among tumors with the highest LOXL3 expression levels. LOXL3 silencing of U87MG cells by siRNA led to the spreading of the tumor cell surface, and the transcriptome analysis of these cells revealed an upregulation of genes coding for extracellular matrix, cell adhesion, and cytoskeleton components, convergent to an increase in cell adhesion and a decrease in cell invasion observed in functional assays. Significant correlations of LOXL3 expression with genes coding for tubulins were observed in the mesenchymal subtype in the TCGA RNA-seq dataset of glioblastoma (GBM). Conversely, genes involved in endocytosis and lysosome formation, along with MAPK-binding proteins related to focal adhesion turnover, were downregulated, which may corroborate the observed decrease in cell viability and increase in the rate of cell death. Invasiveness is a major determinant of the recurrence and poor outcome of GBM patients, and downregulation of LOXL3 may contribute to halting the tumor cell invasion.

【 授权许可】

Unknown