Tumor Type-Dependent Function of the Par3 Polarity Protein in Skin Tumorigenesis
Tumor Type-Dependent Function of the Par3 Polarity Protein in Skin Tumorigenesis
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DOI：
10.1016/j.ccr.2012.08.004
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发表时间：
2012-09-11
期刊：
影响因子：
50.3
通讯作者：
Collard, John G.
中科院分区：
文献类型：
--
作者：
Iden, Sandra;van Riel, Wilhelmina E.;Collard, John G.
细胞极化在发育和组织动态平衡过程中是至关重要的，并受Scribble、Crumbs和PAR复合体的保守蛋白调节。在小鼠皮肤肿瘤的发生中，Par3缺乏会导致乳头状瘤的形成和生长减少。Par3通过调节生长和存活来介导其促肿瘤活性，因为在体内和体外，Par3缺失增加了细胞凋亡并减少了生长。相比之下，Par3基因缺陷的小鼠更容易形成角化棘皮瘤，角化棘皮瘤是一种皮肤肿瘤，被认为来自不同的细胞来源，经常在人类中观察到。在小鼠和人类角化棘皮瘤中，PAR3的表达都降低，表明PAR3具有肿瘤抑制特性。我们的结果确定了PAR3在皮肤癌中的双重功能，根据肿瘤类型的不同，既有促肿瘤活性，也有肿瘤抑制活性。
Cell polarization is crucial during development and tissue homeostasis and is regulated by conserved proteins of the Scribble, Crumbs, and Par complexes. In mouse skin tumorigenesis, Par3 deficiency results in reduced papilloma formation and growth. Par3 mediates its tumor-promoting activity through regulation of growth and survival, since Par3 deletion increases apoptosis and reduces growth in vivo and in vitro. In contrast, Par3-deficient mice are predisposed to formation of keratoacanthomas, cutaneous tumors thought to originate from different cellular origin and frequently observed in humans. Par3 expression is reduced in both mouse and human keratoacanthomas, indicating tumor-suppressive properties of Par3. Our results identify a dual function of Par3 in skin cancer, with both pro-oncogenic and tumor-suppressive activity depending on the tumor type.