CEACAM6 cross-linking induces caveolin-1-dependent, Src-mediated focal adhesion kinase phosphorylation in BxPC3 pancreatic adenocarcinoma cells (Retracted Article)
CEACAM6 cross-linking induces caveolin-1-dependent, Src-mediated focal adhesion kinase phosphorylation in BxPC3 pancreatic adenocarcinoma cells (Retracted Article)
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DOI：
10.1074/jbc.m402051200
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发表时间：
2004-05-28
影响因子：
4.8
通讯作者：
Whang, EE
中科院分区：
文献类型：
--
作者：
Duxbury, MS;Ito, H;Whang, EE
尽管缺乏跨膜或细胞内结构域，糖基磷脂酰肌醇锚定蛋白可以调节细胞内的信号事件，在许多情况下是通过聚集在膜“脂筏”微域内。CEACAM6是一种糖基化磷脂酰肌醇连接的细胞表面蛋白，在胰腺癌细胞的非锚定生存和转移中起重要作用。我们检测了CEACAM6抗体介导的交联剂对CEACAM6过表达的胰腺导管腺癌细胞系BxPC3细胞内信号事件和锚定非依赖生存的影响。CEACAM6交联剂可增加c-Src的活性，并诱导粘着斑激酶p125(FAK)酪氨酸磷酸化。粘着斑激酶的磷酸化依赖于c-Src激酶的激活，而这需要小窝蛋白-1的参与。CEACAM6交联物诱导细胞对失巢凋亡的抵抗力显著增加。这些观察代表了这种重要的细胞表面癌蛋白影响细胞内信号事件从而影响恶性细胞行为的机制的第一个表征。
Despite lacking transmembrane or intracellular domains, glycosylphosphatidylinositol-anchored proteins can modulate intracellular signaling events, in many cases through aggregation within membrane "lipid raft" microdomains. CEACAM6 is a glycosylphosphatidylinositol-linked cell surface protein of importance in the anchorage-independent survival and metastasis of pancreatic adenocarcinoma cells. We examined the effects of antibody-mediated cross-linking of CEACAM6 on intracellular signaling events and anchorage-independent survival of the CEACAM6-overexpressing pancreatic ductal adenocarcinoma cell line, BxPC3. CEACAM6 cross-linking increased c-Src activation and induced tyrosine phosphorylation of p125(FAK) focal adhesion kinase. Focal adhesion kinase phosphorylation was dependent on c-Src kinase activation, for which caveolin-1 was required. CEACAM6 cross-linking induced a significant increase in cellular resistance to anoikis. These observations represent the first characterization of the mechanism through which this important cell surface oncoprotein influences intracellular signaling events and hence malignant cellular behavior.