TGF-β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways.
TGF-β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways.
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TGF-β 反式激活 EGFR，并通过经典的 Smad3 和 ERK/Sp1 信号通路促进乳腺癌迁移和侵袭
DOI：
10.1002/1878-0261.12162
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发表时间：
2018-03
影响因子：
6.6
通讯作者：
Niu R
中科院分区：
文献类型：
--
作者：
Zhao Y;Ma J;Fan Y;Wang Z;Tian R;Ji W;Zhang F;Niu R
转化生长因子-β（TGF-β）在乳腺癌的早期阶段作为一种有效的增殖抑制剂和凋亡诱导剂，但在晚期阶段促进癌症的侵袭性。TGF-β对癌症发展的双重作用被称为TGF-β悖论，TGF-β的显着功能转换是一个关键和有争议的现象，已被广泛研究了几十年。这种现象可能归因于TGF-β信号传导与其他途径之间的串扰，包括癌症进展期间的EGF受体（EGFR）信号传导。然而，TGF-β将其作用从肿瘤抑制因子转变为癌症促进因子的潜在机制仍然难以捉摸。在这项研究中，TGF-β与乳腺癌组织中的EGFR表达呈正相关，并且在乳腺癌细胞系中观察到TGF-β信号传导与EGFR反式激活之间的功能联系。TGF-β促进乳腺癌细胞的迁移和侵袭能力，沿着EGFR表达的增加。EGFR对于TGF-β诱导的乳腺癌细胞这些能力的增强也是必不可少的。经典Smad 3信号通路和ERK/Sp1信号通路介导TGF-β诱导的EGFR上调。因此，我们的研究为TGF-β支持乳腺癌进展的新机制提供了见解。
Transforming growth factor‐beta (TGF‐β) functions as a potent proliferation inhibitor and apoptosis inducer in the early stages of breast cancer, yet promotes cancer aggressiveness in the advanced stages. The dual effect of TGF‐β on cancer development is known as TGF‐β paradox, and the remarkable functional conversion of TGF‐β is a pivotal and controversial phenomenon that has been widely investigated for decades. This phenomenon may be attributed to the cross talk between TGF‐β signaling and other pathways, including EGF receptor (EGFR) signaling during cancer progression. However, the underlying mechanism by which TGF‐β shifts its role from a tumor suppressor to a cancer promoter remains elusive. In this study, TGF‐β is positively correlated with EGFR expression in breast cancer tissues, and a functional linkage is observed between TGF‐β signaling and EGFR transactivation in breast cancer cell lines. TGF‐β promotes the migration and invasion abilities of breast cancer cells, along with the increase in EGFR expression. EGFR is also essential for TGF‐β‐induced enhancement of these abilities of breast cancer cells. Canonical Smad3 signaling and ERK/Sp1 signaling pathways mediate TGF‐β‐induced EGFR upregulation. Hence, our study provided insights into a novel mechanism by which TGF‐β supports breast cancer progression.
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影响因子：
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作者：
Deckers, M;van Dinther, M;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
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作者：
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作者：
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通讯作者：
Otto, HF