转移
外渗
结直肠癌
克拉斯
癌症研究
肺
下调和上调
MAPK/ERK通路
细胞因子
癌症
生物
肝癌
肺癌
免疫学
信号转导
医学
病理
细胞生物学
内科学
生物化学
基因
肝细胞癌
作者
Jelena Urosevic,Xabier García-Albéniz,Evarist Planet,Sebastián Real,María Virtudes Céspedes,Marc Guiu,Esther Fernández,Anna Bellmunt,Sylwia Gawrzak,Milica Pavlović,Ramón Mangues,Ignacio Dolado,Francisco M. Barriga,Cristina Nadal,Nancy Kemeny,Eduard Batlle,Ángel R. Nebreda,Roger R. Gomis
摘要
The mechanisms that allow colon cancer cells to form liver and lung metastases, and whether KRAS mutation influences where and when metastasis occurs, are unknown. We provide clinical and molecular evidence showing that different MAPK signalling pathways are implicated in this process. Whereas ERK2 activation provides colon cancer cells with the ability to seed and colonize the liver, reduced p38 MAPK signalling endows cancer cells with the ability to form lung metastasis from previously established liver lesions. Downregulation of p38 MAPK signalling results in increased expression of the cytokine PTHLH, which contributes to colon cancer cell extravasation to the lung by inducing caspase-independent death in endothelial cells of the lung microvasculature. The concerted acquisition of metastatic traits in the colon cancer cells together with the sequential colonization of liver and lung highlights the importance of metastatic lesions as a platform for further dissemination.
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