ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human gastric cancer cells

Hongmei Chen; Lei Zhang; Wenting He; Tao Liu; Yang Zhao; Hao Chen; Yumin Li

doi:10.1016/j.bbrc.2018.01.048

ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human gastric cancer cells

Biochem Biophys Res Commun. 2018 Feb 5;496(2):475-481. doi: 10.1016/j.bbrc.2018.01.048. Epub 2018 Jan 9.

Authors

Hongmei Chen¹, Lei Zhang², Wenting He³, Tao Liu⁴, Yang Zhao⁵, Hao Chen⁶, Yumin Li⁷

Affiliations

¹ Institute of Cell Biology, School of Life Sciences, Lanzhou University, 222 Tian-Shui South Road, Lanzhou 730000, Gansu, China; Institute of Medical Physiology and Psychology, School of Basic Medical Sciences, Lanzhou University, 199 Dong-Gang West Road, Lanzhou 730000, Gansu, China. Electronic address: hmchen@lzu.edu.cn.
² Department of General Surgery, The First Hospital of Lanzhou University, 1 Dong-Gang West Road, Lanzhou 730000, Gansu, China. Electronic address: 13993181644@139.com.
³ Second Hospital of Lanzhou University, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China; Key Laboratory of Digestive Tumor of Gansu Province, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China. Electronic address: hewt03@163.com.
⁴ Second Hospital of Lanzhou University, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China; Key Laboratory of Digestive Tumor of Gansu Province, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China. Electronic address: ldyyliutao@163.com.
⁵ Second Hospital of Lanzhou University, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China; Key Laboratory of Digestive Tumor of Gansu Province, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China. Electronic address: zhaoyang0931@126.com.
⁶ Second Hospital of Lanzhou University, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China; Key Laboratory of Digestive Tumor of Gansu Province, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China. Electronic address: chenhao3996913@163.com.
⁷ Institute of Cell Biology, School of Life Sciences, Lanzhou University, 222 Tian-Shui South Road, Lanzhou 730000, Gansu, China; Second Hospital of Lanzhou University, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China; Key Laboratory of Digestive Tumor of Gansu Province, 82 Cui-Yin Door, Lanzhou 730030, Gansu, China. Electronic address: liym@lzu.edu.cn.

PMID: 29330052
DOI: 10.1016/j.bbrc.2018.01.048

Abstract

Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion regulation and genomic stability, has not been studied in human gastric cancer (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited cell proliferation and induced cell apoptosis in vitro and suppressed tumor xenograft development in vivo. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) was activated following the suppression of its downstream targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase 1 (p70S6K1), and this result was consistent with p53 activation. Significantly, co-immunoprecipitation (Co-IP) analyses indicated that ESCO2 can interact with p53 in GC cells. Taken together, our data demonstrate that ESCO2 is essential for the development of GC and might be a potential therapeutic target for treating GC.

Keywords: Apoptosis; ESCO2; Gastric cancer; Proliferation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / genetics
AMP-Activated Protein Kinases / metabolism
Acetyltransferases / antagonists & inhibitors
Acetyltransferases / genetics*
Acetyltransferases / metabolism
Animals
Apoptosis / genetics
Cell Line, Tumor
Cell Proliferation
Chromosomal Proteins, Non-Histone / antagonists & inhibitors
Chromosomal Proteins, Non-Histone / genetics*
Chromosomal Proteins, Non-Histone / metabolism
Epithelial Cells / metabolism*
Epithelial Cells / pathology
Female
Gene Expression Regulation, Neoplastic*
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Protein Binding
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Ribosomal Protein S6 Kinases, 70-kDa / genetics
Ribosomal Protein S6 Kinases, 70-kDa / metabolism
Signal Transduction
Stomach Neoplasms / genetics*
Stomach Neoplasms / metabolism
Stomach Neoplasms / pathology
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism
Tumor Suppressor Protein p53 / genetics*
Tumor Suppressor Protein p53 / metabolism
Xenograft Model Antitumor Assays

Substances

Chromosomal Proteins, Non-Histone
RNA, Small Interfering
Tumor Suppressor Protein p53
Acetyltransferases
ESCO2 protein, human
MTOR protein, human
Ribosomal Protein S6 Kinases, 70-kDa
TOR Serine-Threonine Kinases
ribosomal protein S6 kinase, 70kD, polypeptide 2
AMP-Activated Protein Kinases
PRKAA1 protein, human