HePTP promotes migration and invasion in triple-negative breast cancer cells via activation of Wnt/β-catenin signaling - 18/09/19
, Chunyang Wang b, 1, Fushun Pan c, 1, Yunqi Liu d, Xianyue Ren b, Huijuan Zeng a, Yawei Shi a, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Graphical abstract |
Highlights |
• | The expression of HePTP was upregulated in TNBC. |
• | HePTP induced metastasis via promotion of cells migration and invasion. |
• | HePTP dephosphorylated GSK3β at Tyr216 and activated Wnt/β-catenin signaling. |
• | HePTP may act as a novel prognostic marker and therapeutic target for TNBC. |
Abstract |
Aim |
Cancer metastasis remains a major challenge for the clinical management of breast cancer, especially triple-negative breast cancer (TNBC), and the underlying molecular mechanisms remain largely unknown. The aim of this study was to explore the mechanism of TNBC metastasis.
Main methods |
The expression of protein tyrosine phosphatase, non-receptor type 7 (HePTP) was detected using real time-PCR, western blot. Wound healing assay and transwell matrix assay were used to evaluate the pro-migration and pro-invasion potential of HePTP in vitro. Luciferase activity assay and nuclear extract analysis were used to evaluate Wnt/β-catenin signaling activity.
Key findings |
We reported that HePTP was overexpressed in TNBC, where it acted to drive migration and invasion of tumor cells. We showed that knockdown of HePTP significantly suppressed metastatic capacity of TNBC cells. Moreover, HePTP promoted cells migration and invasion by dephosphorylating glycogen synthase kinase 3 beta (GSK3β), thereby activating Wnt/β-catenin signaling. Additionally, we demonstrated that overexpression of HePTP in HePTP lowly expressed cells could effectively promote the migration and invasion of breast cancer cells.
Significance |
Our results suggest that HePTP plays a key role in the metastasis of TNBC via activating Wnt/β-catenin signaling. Hence, we propose that HePTP may serve as a novel prognostic marker and a potential therapeutic target for the treatment of TNBC.
Le texte complet de cet article est disponible en PDF.Abbreviations : real time-PCR, MMP7, SNAI2, MMP2, CD44, ERK, p38, GAPDH, p84, SD, SDS/PAGE
Keywords : HePTP, Triple-negative breast cancer, Wnt/β-catenin, Migration, Invasion
Plan
Vol 118
Article 109361- octobre 2019 Retour au numéro
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