Department of Orofacial Sciences, University of California, San Francisco, CA 94143-0422, USA.
Anticancer Res. 2011 Apr;31(4):1205-9.
This study shows that the expression of the extracellular matrix metalloproteinase inducer (EMMPRIN) in oral squamous cell carcinoma cells (SCC) depends upon activation of the Src Family kinaseFyn; and that EMMPRIN and β6 form a complex that requires active Fyn and the full length β6 integrin cytoplasmic domain. Fyn is also important for matrix remodeling as it regulates both matrix type 1 metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-1 and -2 (TIMP1/2). The tumor promoter/suppressor caveolin-1, which associates with MT1-MMP, also requires FYN activation for expression. Lastly, EMMPRIN expression can act as a readout for the mitogen-activated protein kinase (MAPK) pathway, since when MAPK is blocked, so is the expression of EMMPRIN. In oral cancer, the activation of FYN occurs post β6 integrin ligand binding. That the activation of FYN drives EMMPRIN expression and several important pathways associated with invasive oral SCC is now demonstrated.
本研究表明，细胞外基质金属蛋白酶诱导因子（EMMPRIN）在口腔鳞状细胞癌细胞（SCC）中的表达取决于 Src 家族激酶 Fyn 的激活；EMMPRIN 和β6 形成一个需要活性 Fyn 和全长β6 整合素胞质结构域的复合物。Fyn 对于基质重塑也很重要，因为它调节基质金属蛋白酶 1（MT1-MMP）和金属蛋白酶组织抑制剂 1 和 2（TIMP1/2）。与 MT1-MMP 相关的肿瘤促进/抑制因子 caveolin-1 也需要 FYN 激活才能表达。最后，EMMPRIN 的表达可以作为丝裂原活化蛋白激酶（MAPK）通路的读出器，因为当 MAPK 被阻断时，EMMPRIN 的表达也被阻断。在口腔癌中，FYN 的激活发生在β6 整合素配体结合之后。现在已经证明，FYN 的激活驱动 EMMPRIN 的表达以及与侵袭性口腔 SCC 相关的几个重要途径。
