Dataset Information

TM4SF19 controls GABP-dependent YAP transcription in head and neck cancer under oxidative stress conditions.

ABSTRACT: Tobacco and alcohol are risk factors for human papillomavirus-negative head and neck squamous cell carcinoma (HPV^- HNSCC), which arises from the mucosal epithelium of the upper aerodigestive tract. Notably, despite the mutagenic potential of smoking, HPV^- HNSCC exhibits a low mutational load directly attributed to smoking, which implies an undefined role of smoking in HPV^- HNSCC. Elevated YAP (Yes-associated protein) mRNA is prevalent in HPV^- HNSCC, irrespective of the YAP gene amplification status, and the mechanism behind this upregulation remains elusive. Here, we report that oxidative stress, induced by major risk factors for HPV^- HNSCC such as tobacco and alcohol, promotes YAP transcription via TM4SF19 (transmembrane 4 L six family member 19). TM4SF19 modulates YAP transcription by interacting with the GABP (Guanine and adenine-binding protein) transcription factor complex. Mechanistically, oxidative stress induces TM4SF19 dimerization and topology inversion in the endoplasmic reticulum membrane, which in turn protects the GABPβ1 subunit from proteasomal degradation. Conversely, depletion of TM4SF19 impairs the survival, proliferation, and migration of HPV^- HNSCC cells, highlighting the potential therapeutic relevance of targeting TM4SF19. Our findings reveal the roles of the key risk factors of HPV^- HNSCC in tumor development via oxidative stress, offering implications for upcoming therapeutic approaches in HPV^- HNSCC.

SUBMITTER: Shin E

PROVIDER: S-EPMC10873613 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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TM4SF19 controls GABP-dependent YAP transcription in head and neck cancer under oxidative stress conditions.

Shin Eunbie E Kwon Yongsoo Y Jung Eunji E Kim Yong Joon YJ Kim Changgon C Hong Semyeong S Kim Joon J

Proceedings of the National Academy of Sciences of the United States of America 20240205 7

Tobacco and alcohol are risk factors for human papillomavirus-negative head and neck squamous cell carcinoma (HPV- HNSCC), which arises from the mucosal epithelium of the upper aerodigestive tract. Notably, despite the mutagenic potential of smoking, HPV- HNSCC exhibits a low mutational load directly attributed to smoking, which implies an undefined role of smoking in HPV- HNSCC. Elevated YAP (Yes-associated protein) mRNA is prevalent in HPV- HN ...[more]

PMID: 38315837

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Project description:Background: The vestibular end organs (semicircular canals, saccule and utricle) monitor head orientation and motion. Vestibular stimulation by means of controlled translations, rotations or tilts of the head represents a routine manoeuvre to test the vestibular apparatus in a laboratory or clinical setting. In diagnostics, it is used to assess oculomotor postural or perceptual responses, whose abnormalities can reveal subclinical vestibular dysfunctions due to pathology, aging or drugs. Objective: The assessment of the vestibular function requires the alignment of the motion stimuli as close as possible with reference axes of the head, for instance the cardinal axes naso-occipital, interaural, cranio-caudal. This is often achieved by using a head restraint, such as a helmet or strap holding the head tightly in a predefined posture that guarantees the alignment described above. However, such restraints may be quite uncomfortable, especially for elderly or claustrophobic patients. Moreover, it might be desirable to test the vestibular function under the more natural conditions in which the head is free to move, as when subjects are tracking a visual target or they are standing erect on the moving platform. Here, we document algorithms that allow delivering motion stimuli aligned with head-fixed axes under head-free conditions. Methods: We implemented and validated these algorithms using a MOOG-6DOF motion platform in two different conditions. 1) The participant kept the head in a resting, fully unrestrained posture, while inter-aural, naso-occipital or cranio-caudal translations were applied. 2) The participant moved the head continuously while a naso-occipital translation was applied. Head and platform motion were monitored in real-time using Vicon. Results: The results for both conditions showed excellent agreement between the theoretical spatio-temporal profile of the motion stimuli and the corresponding profile of actual motion as measured in real-time. Conclusion: We propose our approach as a safe, non-intrusive method to test the vestibular system under the natural head-free conditions required by the experiential perspective of the patients.

Dataset Information

TM4SF19 controls GABP-dependent YAP transcription in head and neck cancer under oxidative stress conditions.

Publications

TM4SF19 controls GABP-dependent <i>YAP</i> transcription in head and neck cancer under oxidative stress conditions.

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