Journal article
Newly identified invasion drivers define the tumor front in oral squamous cell carcinoma
Cell death discovery
06/20/2026
DOI: 10.1038/s41420-026-03202-y
PMID: 42323321
Abstract
Cells at the invasive front of oral squamous cell carcinoma (OSCC) occupy a partial epithelial-to-mesenchymal transition (p-EMT) state that drives invasion and therapeutic resistance yet remains poorly understood. To define the regulators of this metastable state, we developed an isogenic OSCC model that captures stable epithelial and p-EMT phenotypes and used it to perform a genome-wide CRISPR invasion screen. This unbiased strategy identified 17 modulators of invasion, most previously unrecognized in cancer and virtually unexplored in OSCC, that converge on cytoskeletal remodeling, adhesion, and epigenetic regulation. Within this network, EDIL3 emerged as a central driver of EMT, invasion, and chemoresistance in head and neck cancer, extending prior reports in other tumor types. Importantly, the invasion signature derived from our screen localized with striking specificity to the tumor invasive front of human OSCC, providing direct clinical validation. Together, these findings reveal a novel, targetable network of transient invasion drivers defining the OSCC tumor front.
Details
- Title: Subtitle
- Newly identified invasion drivers define the tumor front in oral squamous cell carcinoma
- Creators
- Guillermo Flores - University of IowaSlyn Uaroon - University of IowaJuan A R Garay - University of Iowa, Holden Comprehensive Cancer CenterMarion Vanneste - Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USAJesse D Riordan - University of IowaAdam J Dupuy - University of IowaKristina W Thiel - University of IowaKaitriana E Colling - University of IowaChristopher S Stipp - University of IowaLi-Chun Lin - University of Iowa, Psychological and Brain SciencesBailey Hollis - Iowa City Public LibraryMariah R Leidinger - University of IowaStephanie J T Chen - University of Iowa, PathologyLillian M Graham - University of Iowa, OtolaryngologyKevin L Knudtson - University of IowaMichael S Chimenti - University of IowaJason A Ratcliff - University of IowaZain Mehdi - University of IowaMadison C McElliott - University of MichiganEric R Anderson - University of IowaMichael D Henry - University of IowaMolly E Heft Neal - University of MichiganJ Chad Brenner - University of MichiganMarisa R Buchakjian - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Cell death discovery
- DOI
- 10.1038/s41420-026-03202-y
- PMID
- 42323321
- NLM abbreviation
- Cell Death Discov
- ISSN
- 2058-7716
- eISSN
- 2058-7716
- Publisher
- Nature
- Grant note
- 5T32DC000040-28 / U.S. Department of Health & Human Services | NIH | National Institute on Deafness and Other Communication Disorders (NIDCD) P30CA086862 / U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics) IRG-21-141-46 / American Cancer Society (American Cancer Society, Inc.)
- Language
- English
- Electronic publication date
- 06/20/2026
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; The University of Iowa Institute for Vision Research; Psychological and Brain Sciences; Pathology; Biology; Obstetrics and Gynecology; Otolaryngology; Holden Comprehensive Cancer Center; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9985176655702771
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