T-lymphoma invasion and metastasis 1 promotes invadopodia formation and is regulated by the PI3K/Akt signaling pathway in hepatocellular carcinoma

T-lymphoma invasion and metastasis 1 promotes invadopodia formation and is regulated by the PI3K/Akt signaling pathway in hepatocellular carcinoma
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DOI:
10.1016/j.yexcr.2021.112806
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发表时间:
2021-09-10
影响因子:
3.7
通讯作者:
Zheng,Shuguo
Zheng,Shuguo
中科院分区:
医学3区
文献类型:
--
作者:
Wang,Baolin;Zheng,Bowen;Zheng,Shuguo

文献摘要

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目前,肝细胞癌(HCC)侵袭和转移的机制仍有许多方面知之甚少。侵袭伪足是癌细胞侵袭和转移的重要结构。我们确定T淋巴瘤侵袭和转移1(Tiam 1)的高表达与HCC侵袭和转移以及手术后患者预后不良相关。功能获得和丧失研究证实Tiam 1通过激活Rac 1促进HCC中侵袭伪足的形成。一系列的生化实验证实了这种作用是由PI 3 K/Akt信号通路调节的。我们还证实了PIP 2促进了这种效应。总之,这些发现揭示Tiam 1在HCC中侵袭伪足形成中起重要作用。
At present, there are still many poorly understood aspects of the mechanisms underlying hepatocellular carcinoma (HCC) invasion and metastasis. Invadopodia are important structures for cancer cell invasion and metastasis. We determined that high T-lymphoma invasion and metastasis 1 (Tiam1) expression is associated with HCC invasion and metastasis and poor patient prognosis after surgery. Gain- and loss-of-function studies confirmed that Tiam1 promotes invadopodia formation in HCC by activating Rac1. A series of biochemical experiments confirmed that this effect is regulated by the PI3K/Akt signaling pathway. We also confirmed that PIP2 facilitates this effect. In summary, these findings reveal that Tiam1 plays an important role in invadopodia formation in HCC.