Mechanism of anchorage independent growth driven by the KRAS oncogene

背景资料。正常的上皮细胞不能在体外不依赖于锚定的条件下生长，而KRAS转化的癌细胞可以在同样的条件下增殖形成肿瘤球体。这种KRAS癌基因驱动锚定非依赖性生长的能力是恶性转化的标志。目的。在这个项目中，我们的目标是研究KRAS癌基因如何使癌细胞在锚定非依赖条件下增殖。我们的目标是研究KRAS介导的信号转导通路，并了解它们如何调节细胞周期和细胞生存。成就。我们已经确定了KRAS突变的癌细胞株，它们严格依赖KRAS进行锚定独立生长。我们已经确定了肿瘤球体培养中致癌KRAS信号的明显特征，这表明了KRAS癌基因在锚定非依赖环境中用于使细胞存活和细胞增殖的新机制。一份描述当前发现的手稿正在准备出版。

BACKGROUND. Whereas normal epithelial cells cannot grow under anchorage independent conditions in vitro, KRAS transformed cancer cells can proliferate to for a tumor sphere under these same conditions. This ability of the KRAS oncogene to drive anchorage independent growth is a hallmark of malignant transformation. PURPOSE. In this project we aim to study how the KRAS oncogene enables cancer cells to proliferate under anchorage independent conditions. We aim to study KRAS mediated signal transduction pathways and understand how they regulate cell cycle and cell survival. ACCOMPLISHMENT. We have identified KRAS mutant cancer cell lines that are strictly dependent on KRAS for anchorage independent growth. We have identified distinct features of oncogenic KRAS signaling in tumor spheroid culture that suggest novel mechanisms by which the KRAS oncogene uses to enable cell survival and cell proliferation in the anchorage independent setting. A manuscript describing out current findings are under preparation for publication.