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Autophagy gene expression profiling identifies a defective microtubule-associated protein light chain 3A mutant in cancer.

Costa, JR; Prak, K; Aldous, S; Gewinner, CA; Ketteler, R; (2016) Autophagy gene expression profiling identifies a defective microtubule-associated protein light chain 3A mutant in cancer. Oncotarget , 7 (27) pp. 41203-41216. 10.18632/oncotarget.9754. Green open access

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Abstract

The cellular stress response autophagy has been implicated in various diseases including neuro-degeneration and cancer. The role of autophagy in cancer is not clearly understood and both tumour promoting and tumour suppressive effects of autophagy have been reported, which complicates the design of therapeutic strategies based on targeting the autophagy pathway. Here, we have systematically analyzed gene expression data for 47 autophagy genes for deletions, amplifications and mutations in various cancers. We found that several cancer types have frequent autophagy gene amplifications, whereas deletions are more frequent in prostate adenocarcinomas. Other cancer types such as glioblastoma and thyroid carcinoma show very few alterations in any of the 47 autophagy genes. Overall, individual autophagy core genes are altered at low frequency in cancer, suggesting that cancer cells require functional autophagy. Some autophagy genes show frequent single base mutations, such as members of the ULK family of protein kinases. Furthermore, we found hotspot mutations in the arginine-rich stretch in MAP1LC3A resulting in reduced cleavage of MAP1LC3A by ATG4B both in vitro and in vivo, suggesting a functional implication of this gene mutation in cancer development.

Type: Article
Title: Autophagy gene expression profiling identifies a defective microtubule-associated protein light chain 3A mutant in cancer.
Open access status: An open access version is available from UCL Discovery
DOI: 10.18632/oncotarget.9754
Publisher version: http://dx.doi.org/10.18632/oncotarget.9754
Language: English
Additional information: All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License. PII: 9754 Copyright @ 2016 Impact Journals, LLC
Keywords: ATG4B, MAP1LC3A R70H, autophagy, gene expression, luciferase release assay
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1499871
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