重编程
转移
糖酵解
癌症研究
生物
癌症
磷酸果糖激酶
乳腺癌
细胞生物学
细胞
酶
遗传学
生物化学
作者
Nan Li,Xinyue Wang,Jie Sun,Ying Li,Anna Han,Zhenhua Lin,Yang Yang
出处
期刊:Carcinogenesis
[Oxford University Press]
日期:2022-05-02
卷期号:43 (7): 705-715
被引量:4
标识
DOI:10.1093/carcin/bgac039
摘要
T lymphoma invasion and metastasis 1 (Tiam1) as a tumor-associated gene specifically activates Rho-like GTPases Rac1 and implicates in the invasive phenotype of many cancers. Altering the glycolytic pathway is foreseen as a sound approach to trigger cancer regression. However, the mechanism of Tiam1 in breast cancer (BC) glycolysis reprogramming remains to be clarified. Here, we reported the Tiam1 high expression and prognostic significance in BC. In vitro and in vivo experimental assays identified the functional role of Tiam1 in promoting BC cell proliferation, metastasis and glycolysis reprogramming. Mechanistically, we showed for the first time that Tiam1 could interact with the crucial glycolytic enzyme phosphofructokinase, liver type (PFKL) and promote the evolution of BC in a PFKL-dependent manner. Moreover, miR-21-5p was found to exacerbate the BC proliferation and aggression by targeting Tiam1. Altogether, our study highlights the critical role of Tiam1 in BC development and that the miR-21-5p/Tiam1/PFKL signaling pathway may serve as a target for new anti-BC therapeutic strategies.
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