Journal article
C-terminal interleukin 1 alpha (IL-1α) overexpression drives EMT and a vulnerability to ferroptosis in HNSCC
Redox biology, Vol.93, 104172
06/01/2026
DOI: 10.1016/j.redox.2026.104172
PMID: 42013543
Abstract
High tumor expression of the cytokine interleukin-1 alpha (IL-1α) is associated with an aggressive tumor phenotype and poor clinical outcomes in head and neck squamous cell carcinoma (HNSCC). However, the mechanism behind IL-1α-induced tumor aggressiveness is unclear. The goal of this work is to investigate the biological consequences of increased IL-1α in HNSCC cells.
Three IL1A constructs (Full-length, N-terminal, and C-terminal [CT]) were transduced into Cal27 HNSCC cells and validated for IL-1α expression. Differences in cell survival, metabolic profiling, epithelial-to-mesenchymal transition (EMT), oxidative stress parameters and response to therapy were compared among the parental and IL-1α overexpressing cell lines.
Overexpression of CT IL-1α (but not the other constructs) led to increased cell proliferation, membrane fluidity, hydroperoxide production, intracellular iron and lipid peroxidation, EMT changes, and a shift toward glutamate utilization compared to control cell lines. Finally, CT IL-1α cells (but not the other constructs) were highly sensitive to the ferroptosis inducer RSL3.
Together this work suggests that increased tumor IL-1α expression triggers a shift toward an oxidative and ferroptotic environment, leading to an aggressive tumor phenotype and drug resistance; but also reveals a unique vulnerability to agents that induce ferroptosis.
Details
- Title: Subtitle
- C-terminal interleukin 1 alpha (IL-1α) overexpression drives EMT and a vulnerability to ferroptosis in HNSCC
- Creators
- Ishrat Nourin Khan - University of IowaKrishna Awasthi - University of IowaZiyu Wang - University of Iowa Hospitals and ClinicsNafis Md Irfan - University of IowaJay Saepoo - University of Iowa Hospitals and ClinicsJoan N. Whittier - University of Iowa Hospitals and ClinicsNurgul Koyuncu - University of IowaMd Roman Mogal - University of IowaM.M. Hasibuzzaman - University of Iowa Hospitals and ClinicsShujie Yang - University of Iowa Hospitals and ClinicsMichael Petronek - University of Iowa Hospitals and ClinicsAndrean L. Simons - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA, USA Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA Free Radical and Radiation Biology Program, Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.93, 104172
- DOI
- 10.1016/j.redox.2026.104172
- PMID
- 42013543
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- Elsevier
- Grant note
- United States ( U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service: 2I01BX004829
This work was funded by Merit Review Award #2I01BX004829 from the United States ( U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service.
- Language
- English
- Electronic publication date
- 04/16/2026
- Date published
- 06/01/2026
- Academic Unit
- Oral Pathology, Radiology and Medicine; Pathology; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology
- Record Identifier
- 9985157608202771
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