title: Asb6 upregulation by Areca nut extracts is associated with betel quid-induced oral carcinogenesis.
abstract: Betel quit (BQ) chewing is a popular habit, especially in southern and southeastern Asia. Areca nut extracts (ANE), the major components of BQ, have been documented to induce reactive oxygen species, and consequently to cause genetic damage. ANE usage is tightly linked to oral cancer; however, the details of the molecular mechanism that results in carcinogenesis remain unclear. Previously, we successfully established HaCaT cells surviving from the long-term exposure of sublethal doses of ANE (Lai KC, Lee TC. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutat Res 2006;599:66-75). Here, we identified the upregulation of Asb6, a coupling protein to the APS adapter protein, which is involved in insulin signaling for glucose transportation, of normal keratinocytes and oral cancer cells under ANE treatment. Immunohistochemical analyses of Asb6 on oral squamous cell carcinoma (OSCC) tissues (n=57) demonstrated the positive correlation between Asb6 upregulation (cancerous tissues versus adjacent normal tissues) and clinicopathological features. We showed that the combination of ANE-enhanced Asb6 expression in vitro and Asb6 upregulation in OSCC patients leads to poor survival status. In conclusion, our results suggest that upregulated Asb6 could act as a prognostic marker for oral cancer.
authors.affiliation: Institute of Oral Biology, National Yang-Ming University, No. 155, Sec. 2, Li-Nong St., Pei-Tou, Taipei, Taiwan, ROC.
authors.forename: Kai-Feng
authors.initials: KF
authors.lastname: Hung
authors.forename: Kuo-Chu
authors.initials: KC
authors.lastname: Lai
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Chung-Ji
authors.initials: CJ
authors.lastname: Liu
authors.forename: Te-Chang
authors.initials: TC
authors.lastname: Lee
authors.forename: Jeng-Fan
authors.initials: JF
authors.lastname: Lo
mesh_terms: D001114:Areca / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D016022:Case-Control Studies; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D010936:Plant Extracts / Q000633:toxicity*; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D013624:Taiwan; D015854:Up-Regulation
chemical_list: C492435:Asb6 protein, mouse; D010936:Plant Extracts; D050826:Suppressor of Cytokine Signaling Proteins