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PLCE1 Promotes Esophageal Cancer Cell Progression by Maintaining the Transcriptional Activity of Snail

Authors :
Shicong Zhai
Cui Liu
Lichen Zhang
Jian Zhu
Jiqiang Guo
Jinghang Zhang
Zhijun Chen
Wenping Zhou
Tingmin Chang
Siguang Xu
Yijun Qi
Ting Zhuang
Na Yu
Weilong Wang
Hui Wang
Sifan Yu
Xiumin Li
Source :
Neoplasia: An International Journal for Oncology Research, Vol 19, Iss 3, Pp 154-164 (2017)
Publication Year :
2017
Publisher :
Elsevier, 2017.

Abstract

Esophageal cancer is among the most deadly malignant diseases. However, the genetic factors contributing to its occurrence are poorly understood. Multiple studies with large clinic-based cohorts revealed that variations of the phospholipase C epsilon (PLCE1) gene were associated with esophageal cancer susceptibility. However, the causative role of PLCE1 in esophageal cancer is not clear. We inactivated the functional alleles of PLCE1 by CRISPR/Cas9 genome editing technology. The resultant PLCE1 inactivated cells were analyzed both in vitro and in vivo. Our results showed that loss of PLCE1 dramatically decreased the invasion and proliferation capacity of esophageal carcinoma cells in vitro. Moreover, such PLCE1 inactivated tumor grafts exhibited significantly decreased tumor size in mice. We found that PLCE1 was required to maintain protein level of snail a key transcription factor responsible for invasion. Our further transcriptomic data revealed that deficient cells were significantly decreased in expression of genes enriched as targets of Snail. Strikingly, recovery of Snail protein at least partially rescued the invasion and proliferation capacity in PLCE1 inactivated cells. In ESCC clinical specimens, PLCE1 was correlated with tumor stage (P

Details

Language :
English
ISSN :
14765586
Volume :
19
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Neoplasia: An International Journal for Oncology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.8b01f102023843ef892a5a9912492dd7
Document Type :
article
Full Text :
https://doi.org/10.1016/j.neo.2016.12.007