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 Resjournal_title
Experimental cell researchauthors
Jing P,Zhou S,Xu P,Cui P,Liu X,Liu X,Liu X,Wang H,Xu Wdoi
10.1016/j.yexcr.2019.111746subject
Has Abstractpub_date
2020-01-15 00:00:00pages
111746issue
2eissn
0014-4827issn
1090-2422pii
S0014-4827(19)30629-9journal_volume
386pub_type
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