Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control
Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control
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DOI：
10.1038/ncb1485
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发表时间：
2006-11-01
影响因子：
21.3
通讯作者：
Muthuswamy, Senthil K.
中科院分区：
文献类型：
--
作者：
Aranda, Victoria;Haire, Teresa;Muthuswamy, Senthil K.
在癌的发展过程中，上皮细胞的极化腺体组织经常丢失。然而，负责极性破坏的特定癌基因靶点尚未确定。在这里，我们证明了ErbB2的激活通过与PAR极性复合体的成分Par6-aPKC结合来破坏顶端-基础极性。抑制Par6和aPKC之间的相互作用可阻断ErbB2破坏乳腺上皮的腺泡组织和保护细胞免于凋亡的能力，但不是细胞增殖所必需的。因此，癌基因以极性蛋白为靶点，扰乱腺体组织，保护细胞在肿瘤发生发展过程中免于凋亡死亡。
The polarized glandular organization of epithelial cells is frequently lost during development of carcinoma. However, the specific oncogene targets responsible for polarity disruption have not been identified. Here, we demonstrate that activation of ErbB2 disrupts apical-basal polarity by associating with Par6-aPKC, components of the Par polarity complex. Inhibition of interaction between Par6 and aPKC blocked the ability of ErbB2 to disrupt the acinar organization of breast epithelia and to protect cells from apoptosis but was not required for cell proliferation. Therefore, oncogenes target polarity proteins to disrupt glandular organization and protect cells from apoptotic death during development of carcinoma.