A minimal fragment of MUC1 mediates growth of cancer cells.
A minimal fragment of MUC1 mediates growth of cancer cells.
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DOI：
10.1371/journal.pone.0002054
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发表时间：
2008-04-30
期刊：
影响因子：
3.7
通讯作者：
Bamdad C
中科院分区：
文献类型：
--
作者：
Mahanta S;Fessler SP;Park J;Bamdad C
MUC1蛋白在许多实体瘤癌症中异常表达。与其在健康上皮细胞上的顶端聚集相反，它均匀地分布在癌细胞上。然而，异常表达和癌症之间的机制联系仍然难以捉摸。在此，我们报告了一种膜结合MUC1切割产物，我们称之为MUC1*，是培养的癌细胞和癌组织上蛋白质的主要形式。此外，我们证明了MUC1的最小片段MUC1*1110的转染，其仅含有细胞外结构域的四十五（45）个氨基酸，足以赋予先前归因于全长蛋白质的致癌活性。通过比较分子量和功能，MUC1* 和MUC1*1110似乎大致相当。证据强烈支持MUC1* 胞外结构域的二聚化激活MAP激酶信号级联并刺激细胞生长的机制。这些发现提出了操纵这种生长机制的方法，用于癌症治疗中的治疗干预。
The MUC1 protein is aberrantly expressed on many solid tumor cancers. In contrast to its apical clustering on healthy epithelial cells, it is uniformly distributed over cancer cells. However, a mechanistic link between aberrant expression and cancer has remained elusive. Herein, we report that a membrane-bound MUC1 cleavage product, that we call MUC1*, is the predominant form of the protein on cultured cancer cells and on cancerous tissues. Further, we demonstrate that transfection of a minimal fragment of MUC1, MUC1*1110, containing a mere forty-five (45) amino acids of the extracellular domain, is sufficient to confer the oncogenic activities that were previously attributed to the full-length protein. By comparison of molecular weight and function, it appears that MUC1* and MUC1*1110 are approximately equivalent. Evidence is presented that strongly supports a mechanism whereby dimerization of the extracellular domain of MUC1* activates the MAP kinase signaling cascade and stimulates cell growth. These findings suggest methods to manipulate this growth mechanism for therapeutic interventions in cancer treatments.
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影响因子：
50.3
作者：
Ren, J;Agata, N;Kufe, D
通讯作者：
Kufe, D
影响因子：
4.8
作者：
RUI, H;LEBRUN, JJ;FARRAR, WL
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影响因子：
4.8
作者：
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通讯作者：
Wreschner, DH
影响因子：
3.4
作者：
Bamdad, C
通讯作者：
Bamdad, C
影响因子：
2.6
作者：
Okabe-Kado, J
通讯作者：
Okabe-Kado, J