Journal article
Growth factor receptor signaling induces mitophagy through epitranscriptomic regulation
Autophagy, Vol.19(3), pp.1034-1035
03/04/2023
DOI: 10.1080/15548627.2022.2114765
PMCID: PMC9980508
PMID: 35980802
Abstract
Aberrant growth factor receptor signaling is among the most common oncogenic drivers in cancer biology. Receptor signaling classically induces cancer growth through signaling cascades that mediate effects largely through transcriptional control. Recently, post-transcriptional RNA modifications, collectively designated as epitranscriptomics, have emerged as a critical layer of dysregulation in cancer biology. We recently reported that PDGFR (platelet-derived growth factor receptor) activity in cancer stem cells (CSCs) derived from glioblastoma patients displays increased post-transcriptional mRNA methylation (N6-methyladenosine [m6A]), which promotes CSC maintenance through regulation of mitophagy. Specifically, PDGF-PDGFRB signaling upregulates the expression of the m6A methyltransferase METTL3, which then decorates the mitophagy regulator OPTN (optineurin) mRNA with m6A, thereby promoting OPTN mRNA degradation. Glioblastomas express lower levels of OPTN than normal brain, and forced expression of OPTN reduces tumor growth, supporting a tumor suppressive role for OPTN. Pharmacological targeting of METTL3 with PDGFR or activation of mitophagy demonstrates a combinatorial benefit. Collectively, our results suggest that upstream regulation of mitophagy in lethal cancers is mediated through growth factor receptor control of post-transcriptional RNA regulation, offering novel therapeutic paradigms.
Details
- Title: Subtitle
- Growth factor receptor signaling induces mitophagy through epitranscriptomic regulation
- Creators
- Deguan Lv - University of Pittsburgh Medical CenterKailin Yang - Cleveland ClinicJeremy N. Rich - University of Pittsburgh Medical Center
- Resource Type
- Journal article
- Publication Details
- Autophagy, Vol.19(3), pp.1034-1035
- Publisher
- Taylor & Francis
- DOI
- 10.1080/15548627.2022.2114765
- PMID
- 35980802
- PMCID
- PMC9980508
- ISSN
- 1554-8627
- eISSN
- 1554-8635
- Number of pages
- 2
- Grant note
- T32CA094186 / Computational Genomic Epidemiology of Cancer (CoGEC) program at Case Comprehensive Cancer Center ASCO Conquer Cancer Foundation RSNA Research Resident Grant CA197718; CA238662; NS103434 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 03/04/2023
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984696722602771
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