ReferenceID 4573
Fat mass and obesity-associated protein regulates arecoline-exposed oral cancer immune response through programmed cell death-ligand 1
Cancer Sci
The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathologic
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4573
- Evidence Id
- 21163
- Core Evidence Id
- 21163
- Source Reference Id
- 2416
- Herb2 Reference Id
- HBREF003213
- Subject Paper Key
- HBIN016699_35289035
- Pubmed Id
- 35289035
- Doi
- 10.1111/cas.15332
- Paper Title
- Fat mass and obesity-associated protein regulates arecoline-exposed oral cancer immune response through programmed cell death-ligand 1
- Paper Abstract
- The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6-methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline-promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity-associated protein (FTO), MYC, and programmed cell death-ligand 1 (PD-L1) in OSCC cells. Moreover, upregulation of PD-L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline-induced FTO promotes the stability and expression levels of PD-L1 transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells. Blockage of PD-L1 by administration of anti-PD-L1 antibody shrinks tumor size and improves mouse survival by elevating T-cell-mediated tumor cell killing. Therefore, targeting PD-L1 might be a potential therapeutic strategy for treating PD-L1-positive OSCC patients, especially those with habitual areca nut chewing.
- Journal
- Cancer Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; patient; oscc cell lines
- Experiment Type
- Clinical & Animal Experiment
- Phenotype Related
- Obesity; Tumor; Oscc Malignance; Cancer; Oral Squamous Cell Carcinoma
- Paper Title Cn
- Paper Title En
- Fat mass and obesity-associated protein regulates arecoline-exposed oral cancer immune response through programmed cell death-ligand 1
- Bilingual Status
- semi_complete