权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular and genetic interaction of the polarity proteins Par3 and aPKC in skin carcinogenesis

极性蛋白 Par3 和 aPKC 在皮肤癌发生中的分子和遗传相互作用

基本信息

批准号：
252588851
负责人：
Professorin Dr. Sandra Iden
金额：
--
依托单位：
Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/252588851?language=en
关键词：
Molecular genetic interaction polarity proteins

项目摘要

Non-melanoma skin cancer is among the most common cancers worldwide with a still increasing incidence due to longer life expectancy and rising sun exposure. Interestingly, the tumor environment plays a decisive role in skin cancer progression. Alterations in polarity and architecture of tumor cells are hallmarks of cancers and have been implicated in cancer growth, invasion and metastasis. The mechanisms that determine how the tumor cyto-architecture and its surroundings communicate to either promote or inhibit cancer are largely unknown. Previously we have identified a crucial role for the polarity proteins aPKCl and Par3, which can form a complex, in the regulation of epidermal stem cell maintenance, keratinocyte differentiation and survival as well as skin inflammation. Most importantly, epidermal inactivation of Par3 inhibits papilloma formation but promotes keratoacanthoma formation. These tumors are thought to arise from different cell populations, indicating a context-dependent role for Par3 in different skin tumors. In the present proposal we will ask whether aPKCl and Par3 have overlapping or different roles in skin tumor promotion and suppression by combining our expertise and different mouse models generated in our laboratories. We will address the underlying mechanisms by which alterations in Par3 and aPKCl control tumor initiation and progression and address how these alterations in tumor cell architecture affect the communication with the microenvironment to either drive or inhibit tumorigenesis.

非黑色素瘤皮肤癌是世界上最常见的癌症之一，由于预期寿命延长和阳光照射，发病率仍在上升。有趣的是，肿瘤环境在皮肤癌的进展中起着决定性的作用。肿瘤细胞的极性和结构的改变是癌症的特征，并与癌症的生长、侵袭和转移有关。决定肿瘤细胞结构和其周围环境如何沟通以促进或抑制癌症的机制在很大程度上是未知的。此前，我们已经确定了极性蛋白aPKCL和Par3在调节表皮干细胞维持、角质形成细胞的分化和存活以及皮肤炎症中起着至关重要的作用。最重要的是，PAR3的表皮失活抑制了乳头状瘤的形成，但促进了角化棘皮瘤的形成。这些肿瘤被认为来自不同的细胞群，表明Par3在不同的皮肤肿瘤中起着上下文依赖的作用。在目前的提案中，我们将结合我们的专业知识和我们实验室培育的不同小鼠模型，询问aPKCL和Par3在促进和抑制皮肤肿瘤方面是否具有重叠或不同的作用。我们将阐述Par3和aPKCL基因改变控制肿瘤启动和进展的潜在机制，以及这些肿瘤细胞结构的改变如何影响与微环境的沟通，从而驱动或抑制肿瘤的发生。