1. Academic Validation
  2. Anchorage-independent cell proliferation promoted by fascin's F-actin bundling

Anchorage-independent cell proliferation promoted by fascin's F-actin bundling

  • bioRxiv. 2024 May 4:2024.05.04.592404. doi: 10.1101/2024.05.04.592404.
Tadamoto Isogai Vasanth Siruvallur Murali Felix Zhou Xinxin Wang Divya Rajendran Lizbeth Perez-Castro Niranjan Venkateswaran Maralice Conacci-Sorrell Gaudenz Danuser
Abstract

The actin filament (F-actin) bundling protein fascin-1 is highly enriched in many metastatic cancers. Fascin's contribution to metastasis have been ascribed to its enhancement of cell migration and invasion. However, mouse genetic studies clearly point to functions also in tumorigenesis, yet without mechanistic underpinnings. Here, we show that fascin expression promotes the formation of a non-canonical signaling complex that enables anchorage-independent proliferation. This complex shares similarities to focal adhesions and we refer to them as pseudo-adhesion signaling scaffolds (PASS). PASS are enriched with tyrosine phosphorylated proteins and require fascin's F-actin-bundling activity for its assembly. PASS serve as hubs for the Rac1/PAK/JNK proliferation signaling axis, driven by PASS-associated Rac-specific GEFs. Experimental disruption of either fascin or RacGEF function abrogates sustained proliferation of aggressive cancers in vitro and in vivo . These results add a new molecular element to the growing arsenal of metabolic and oncogenic signaling programs regulated by the Cytoskeleton architecture.

Figures
Products
我们的 Cookie 政策

我们使用 Cookies 和类似技术以提高网站的性能和提升您的浏览体验,部分功能也使用 Cookies 帮助我们更好地理解您的需求,为您提供相关的服务。 如果您有任何关于我们如何处理您个人信息的疑问,请阅读我们的《隐私声明》