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TGF-? transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways.


ABSTRACT: Transforming growth factor-beta (TGF-?) 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-? on cancer development is known as TGF-? paradox, and the remarkable functional conversion of TGF-? is a pivotal and controversial phenomenon that has been widely investigated for decades. This phenomenon may be attributed to the cross talk between TGF-? signaling and other pathways, including EGF receptor (EGFR) signaling during cancer progression. However, the underlying mechanism by which TGF-? shifts its role from a tumor suppressor to a cancer promoter remains elusive. In this study, TGF-? is positively correlated with EGFR expression in breast cancer tissues, and a functional linkage is observed between TGF-? signaling and EGFR transactivation in breast cancer cell lines. TGF-? promotes the migration and invasion abilities of breast cancer cells, along with the increase in EGFR expression. EGFR is also essential for TGF-?-induced enhancement of these abilities of breast cancer cells. Canonical Smad3 signaling and ERK/Sp1 signaling pathways mediate TGF-?-induced EGFR upregulation. Hence, our study provided insights into a novel mechanism by which TGF-? supports breast cancer progression.

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC5830653 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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TGF-β transactivates EGFR and facilitates breast cancer migration and invasion through canonical Smad3 and ERK/Sp1 signaling pathways.

Zhao Yuanyuan Y   Ma Jing J   Fan Yanling Y   Wang Zhiyong Z   Tian Ran R   Ji Wei W   Zhang Fei F   Niu Ruifang R  

Molecular oncology 20180124 3


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 ot  ...[more]

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