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PSMD7 downregulation induces apoptosis and suppresses tumorigenesis of esophageal squamous cell carcinoma <italic>via</italic> the mTOR/p70S6K pathway.

Authors :
Shi, Ke
Zhang, Jin‐zhong
Zhao, Rui‐li
Yang, Liang
Guo, Dan
Source :
FEBS Open Bio; Apr2018, Vol. 8 Issue 4, p533-543, 11p
Publication Year :
2018

Abstract

PSMD7, a 19S proteasome subunit, is overexpressed in most carcinoma cells. It forms a dimer with PSMD14 that functions in the removal of attached ubiquitin chain. However, there is little knowledge about the cellular mechanism of PSMD7 and its exact biological function, especially in cancer cells. In this study, we explored the role of PSMD7 in proliferation, cell cycle, apoptosis, and proteasomal proteolysis in the esophageal squamous cell carcinoma (ESCC) cell line EC9706. Our results showed that PSMD7 was highly expressed in ESCC cells. Downregulation of PSMD7 by lentivirus‐mediated shRNA led to decreased proliferation, increased cell apoptosis, and reduced proteasomal function. Notably, lower expression level of mTOR and p70S6K and suppressed activity of mTOR/p70S6K pathway were detected after PSMD7 downregulation. By contrast, increased expression of p‐mTOR&lt;superscript&gt;Ser2448&lt;/superscript&gt; and p‐p70S6K&lt;superscript&gt;Thr421/Ser424&lt;/superscript&gt; was discovered upon PSMD7 overexpression in Het‐1A cells. Furthermore, PSMD7 downregulation contributed to decelerated tumor growth, inhibition of proteasomal function, induced cell apoptosis and attenuated activity of mTOR/p70S6K pathway &lt;italic&gt;in&#160;vivo&lt;/italic&gt;. These findings suggest that PSMD7 and the mTOR/p70S6K pathway may be a promising candidate for developing therapies for ESCC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
22115463
Volume :
8
Issue :
4
Database :
Supplemental Index
Journal :
FEBS Open Bio
Publication Type :
Academic Journal
Accession number :
128865517
Full Text :
https://doi.org/10.1002/2211-5463.12394