Abstract PO-100: <i>Fusobacterium nucleatum</i> promotes epithelial-mesenchymal transition (EMT) of oral squamous cell carcinoma (OSCC) via INHBA-dependent SMAD/Laminin332/PI3K/AKT pathway
Bibliographic record
Abstract
Abstract Introduction The enrichment of Fusobacterium nucleatum has been reported in both oral rinses and lesion samples from oral squamous cell carcinoma (OSCC) patients based on several case-control sequencing analyses, but studies on the potential role of F. nucleatum in OSCC tumorigenesis are still limited. In this study, we sought to elucidate the relationship between F. nucleatum and host transcriptome dysregulation in potentially carcinogenic pathways. Method The association between microbiota dysbiosis and host gene transcriptome was profiled by bacterial 16S rRNA V3-V4 amplicon sequencing and host gene long non-coding RNA sequencing (lncRNA-seq) for tumor and adjacent normal (AN) tissues from OSCC patients. Cell migration and invasion assays were performed using the in vitro bacteria-cell co-culture model. EMT-related molecular mechanisms induced by F. nucleatum were further validated by IncRNA-seq, real-time PCR, and western blot for bacteria-infected cells, respectively, at the genetic and proteomic levels. Result Significant enrichment of Fusobacterium was observed in OSCC tumor samples when compared to the paired AN samples. Correlation analysis between mucosal oral bacteria and host transcriptome in the OSCC tumor microenvironment elucidated the positive relationship between Fusobacterium and EMT pathways including significantly upregulated genes INHBA, SNAI2, and LAMC2. Using in-vitro cell models, we further observed that F. nucleatum significantly promoted cell migration and invasion, and significantly dysregulated the expression of several EMT factors including the increased inducer inhibin beta A (INHBA), core regulators SNAI1 (snai1) and SLUG (snai2), effectors vimentin (VIM) and N-cadherin (CDH2), and decreased E-cadherin (CDH1). Following the INHBA/SMAD pathway induced by F. nucleatum infection, the expression of an essential extracellular matrix glycoprotein, Laminin 332, was dramatically enhanced, which may trigger the phosphorylation of phosphatidylinositol 3-kinase and AKT kinase in the downstream PI3K/AKT pathway for the promoted cell migration and invasion ability. Conclusion Our study confirms the enrichment of Fusobacterium in the OSCC tumor microenvironment and reveals that F. nucleatum infection induces the INHBA/SAMD pathway and subsequently increases Laminin 332 expression, which may further promote the phosphorylation of PI3K/AKT and enhance OSCC migration and invasion. Citation Format: Hengyan Zhu, Liuyang Cai, Zigui Chen, Jason Y. K. Chan. Fusobacterium nucleatum promotes epithelial-mesenchymal transition (EMT) of oral squamous cell carcinoma (OSCC) via INHBA-dependent SMAD/Laminin332/PI3K/AKT pathway [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-100.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".