PDK1 promotes metastasis by inducing epithelial-mesenchymal transition in hypopharyngeal carcinoma via the Notch1 signaling pathway.

Abstract:

:Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare malignancy and has the worst prognosis among head and neck cancer. Metastasis is the major cause of poor prognosis in HSCC patients. In this study, we found that 3-phosphoinositide-dependent protein kinase 1 (PDK1 or PDPK1) was overexpressed in HSCC. The overexpression was positively correlated lymph node metastasis, clinical stage, and distant metastasis and indicated poor outcome. Loss and gain-of-function revealed that PDK1 increased cell proliferation, migration and invasion in vitro as well as tumor growth and metastasis in vivo. Mechanically, PDK1 induced epithelial-mesenchymal transition and promoted metastasis by activating the Notch1 signaling pathway. We further illustrated that PDK1 bound with the Notch1 intracellular domain, thereby inhibiting its ubiquitin-mediated degradation in a protein kinase B (Akt-) independent manner. In summary, PDK1/Notch1 axis played an important role in HSCC metastasis, and this investigation provided a new perspective on potential therapeutic targets for HSCC.

journal_name

Exp Cell Res

authors

Jing P,Zhou S,Xu P,Cui P,Liu X,Liu X,Liu X,Wang H,Xu W

doi

10.1016/j.yexcr.2019.111746

subject

Has Abstract

pub_date

2020-01-15 00:00:00

pages

111746

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(19)30629-9

journal_volume

386

pub_type

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