The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Culture Conditions
2.2. Metabolomic Analysis
2.2.1. Cell Collection and Metabolite Extraction
2.2.2. Nuclear Magnetic Resonance (NMR) Spectroscopy and Data Analysis
2.2.3. Mass Spectrometry (MS) and Data Analysis
2.3. Translation and Proliferation Assays
2.4. Immunofluorescence (IF)
2.5. BCA and Western Blot Analysis
2.6. CellTiter-Fluor Viability Assay
2.7. Statstical Analysis
3. Results
3.1. FA Pathway Loss in HNSCC Cells Increases Total Protein and Amino Acid Levels
3.2. FA Pathway Loss Increases Translation and Activates mTOR Signaling in HNSCC Cells
3.3. Rapamycin Suppresses Protein Translation in FA− Deficient HNSCC Cells
3.4. Rapamycin Inhibits FA− HNS Cell Growth Under Nutrient-Depleted Conditions
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
2D | Two-dimensional |
3D | Three-dimensional |
4E-BP1 | 4E binding protein 1 |
AML | Acute myeloid leukemia |
ANOVA | Analysis of variance |
BCA | Bicinchoninic acid |
BSA | Bovine serum albumin |
CC3 | Cleaved caspase-3 |
D2sh | Short-hairpin RNA-treated cells targeted for FANCD2 |
DDR | DNA damage response |
EdU | 5-ethynyl-2′-deoxyuridine; a nucleotide analog used to quantify cellular proliferation |
eIF4/2 | Eukaryotic initiation factor-4 or -2 |
EMT | Epithelial-to-mesenchymal transition |
ESI | Electrospray ionization |
FA | Fanconi anemia; a genetic disease and DNA repair pathway |
FA+ | Fanconi anemia pathway-proficient; indicates cells have a functional FA pathway |
FA− | Fanconi anemia pathway-deficient; indicates cells have a nonfunctional FA pathway |
GSD | Global spectra deconvolution |
HMDB | Human Metabolome Database |
HNSCC | Head and neck squamous cell carcinoma |
HPG | L-homopropargylglycine; a methionine analog used to quantify cellular translation |
HR | Homologous recombination |
HSQC | Heteronuclear single quantum correlation |
ICL | DNA interstrand crosslinks |
ID2 kDa | The FANCI/FANCD2 intermediate complex in the Fanconi anemia pathway kilodalton |
mTOR | Mechanistic target of rapamycin |
MS | Mass spectrometry |
NIKS | Normal immortalized keratinocytes |
NMR | Nuclear magnetic resonance |
NOKS | Normal oral mucosal keratinocytes |
NTsh | Non-targeting short-hairpin RNA-treated cells |
PBS | Phosphate-buffered saline |
PFA | Paraformaldehyde |
PPARγ | Peroxisome proliferator-activated receptor-γ |
RIPA | Radioimmunoprecipitation assay |
SCC | Squamous cell carcinoma |
TBST | Tris-buffered saline with Tween 20 |
TSP | Trimethylsilyl propionic acid-d4 sodium salt |
UHPLC | Ultra-high performance liquid chromatography |
WGA | Wheat germ agglutinin |
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Ruffolo, B.; Vicente-Muñoz, S.; Mehta, K.Y.; Rivera-Cruz, C.M.; Zhao, X.; Romick, L.; Setchell, K.D.R.; Lane, A.; Wells, S.I. The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells. Cancers 2025, 17, 2583. https://doi.org/10.3390/cancers17152583
Ruffolo B, Vicente-Muñoz S, Mehta KY, Rivera-Cruz CM, Zhao X, Romick L, Setchell KDR, Lane A, Wells SI. The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells. Cancers. 2025; 17(15):2583. https://doi.org/10.3390/cancers17152583
Chicago/Turabian StyleRuffolo, Bianca, Sara Vicente-Muñoz, Khyati Y. Mehta, Cosette M. Rivera-Cruz, Xueheng Zhao, Lindsey Romick, Kenneth D. R. Setchell, Adam Lane, and Susanne I. Wells. 2025. "The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells" Cancers 17, no. 15: 2583. https://doi.org/10.3390/cancers17152583
APA StyleRuffolo, B., Vicente-Muñoz, S., Mehta, K. Y., Rivera-Cruz, C. M., Zhao, X., Romick, L., Setchell, K. D. R., Lane, A., & Wells, S. I. (2025). The Fanconi Anemia Pathway Inhibits mTOR Signaling and Prevents Accelerated Translation in Head and Neck Cancer Cells. Cancers, 17(15), 2583. https://doi.org/10.3390/cancers17152583