Bibliographic Details
| Title: |
Discovery of LAMP-2A as potential biomarkers for glioblastoma development by modulating apoptosis through N-CoR degradation |
| Authors: |
Yongjie Wang, Buyi Zhang, Jianli Wang, Haijian Wu, Shenbin Xu, Jianmin Zhang, Lin Wang |
| Source: |
Cell Communication and Signaling, Vol 19, Iss 1, Pp 1-18 (2021) |
| Publisher Information: |
BMC, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Medicine
LCC:Cytology |
| Subject Terms: |
Glioblastoma, LAMP-2A, Chaperone-mediated autophagy, Nuclear receptor co-repressor, Unfolded protein response, Apoptosis, Medicine, Cytology, QH573-671 |
| More Details: |
Abstract Background Lysosome-associated membrane protein type 2A (LAMP-2A) is the key component of chaperone-mediated autophagy (CMA), a cargo-selective lysosomal degradation pathway. Aberrant LAMP-2A expression and CMA activation have been demonstrated in various human malignancies. The study focusing on the intrinsic role of LAMP-2A and CMA in glioblastoma (GBM), and downstream mechanism could provide valuable insight into the pathogenesis and novel therapeutic modality of GBM. Methods The levels of LAMP-2A, nuclear receptor co-repressor (N-CoR), unfolded protein response (UPR) and apoptosis were examined in clinical samples. LAMP-2A siRNA and shRNA were constructed to manipulate CMA activation. The role of CMA and downstream mechanism through degradation of N-CoR and arresting UPR mediated apoptosis were explored in GBM cells and nude mouse xenograft model. Results Elevated LAMP-2A and associated decreased N-CoR expression were observed in GBM as compared with peritumoral region and low-grade glioma. Inhibited UPR and apoptosis were observed in GBM with high LAMP-2A expression. In vitro study demonstrated co-localization and interaction between LAMP-2A and N-CoR. LAMP-2A silencing up-regulated N-CoR and aroused UPR pathway, leading to apoptosis, while N-CoR silencing led to an opposite result. In vivo study further confirmed that LAMP-2A inhibition arrested tumor growth by promoting apoptosis. Conclusions Our results demonstrated the central role of CMA in mediating N-CoR degradation and protecting GBM cells against UPR and apoptosis, and provided evidence of LAMP-2A as potential biomarker. Further research focusing on CMA with other tumorigenic process is needed and selective modulators of LAMP-2A remain to be investigated to provide a novel therapeutic strategy for GBM. Video Abstract. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1478-811X |
| Relation: |
https://doaj.org/toc/1478-811X |
| DOI: |
10.1186/s12964-021-00729-8 |
| Access URL: |
https://doaj.org/article/c066591a449944aaa1ed047f5b9fd438 |
| Accession Number: |
edsdoj.066591a449944aaa1ed047f5b9fd438 |
| Database: |
Directory of Open Access Journals |
