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Involvement of the A disintegrin and metalloproteinase 9 in oral cancer cell invasion
Author(s) -
Buranaphatthana Worakanya,
Wu Shuangjiang,
Makeudom Anupong,
Sastraruji Thanapat,
Supanchart Chayarop,
Krisanaprakornkit Suttichai
Publication year - 2021
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/eos.12775
Subject(s) - disintegrin , small interfering rna , protein kinase b , cancer research , biology , cancer cell , cell growth , cancer , gene knockdown , phosphorylation , metalloproteinase , microbiology and biotechnology , cell culture , transfection , matrix metalloproteinase , biochemistry , genetics
The aims of this study were to determine the functional roles of the transmembrane glycoprotein, Disintegrin and metalloproteinase domain‐containing protein 9 (ADAM 9), in the phosphorylation of epidermal growth factor receptor (EGFR) and AKT and in the aggressiveness of oral cancer cells. Immunohistochemistry and immunoblotting were conducted to determine expression of ADAM 9 and the levels of EGFR phosphorylated at the tyrosine 1173 residue (p‐EGFR tyr1173 ) and AKT phosphorylated at the serine 473 residue (p‐AKT ser473 ) in oral cancer tissues and in the oral cancer cell lines HN5, HN6, HN15, and HN008. Small interfering RNA (siRNA) was used to inhibit expression of ADAM9 mRNA, and thus production of ADAM9 protein, in oral cancer cells. ADAM9‐knockdown cells were examined for p‐EGFR tyr1173 and p‐AKT ser473 levels and used for cell proliferation and invasion assays. A positive correlation among overexpression of ADAM 9, p‐EGFR tyr1173 , and p‐AKT ser473 was found in oral cancer tissues. These biomolecules were also overexpressed in HN6 and HN15 cell lines. Expression of ADAM9 in HN6 and HN15 cells was statistically significantly inhibited by siRNA against ADAM9 mRNA (siADAM9) compared with the negative‐control siRNA (scramble). The levels of p‐AKT ser473 , but not those of p‐EGFR tyr1173 , were statistically significantly blocked by siADAM9. Although the proliferation rates of ADAM9 knocked‐down HN6 and HN15 cells did not differ from those of cells exposed to scramble, a statistically significant decrease in cell invasion was found in these ADAM9 ‐silenced cells. These results suggest a functional role of the ADAM 9/AKT signaling pathway in oral cancer cell invasion, which may be beneficial as a therapeutic target of oral cancer.