CBX3 accelerates the malignant progression of glioblastoma multiforme by stabilizing EGFR expression

作者全名："Peng, Wen; Shi, Shuang; Zhong, Jiacheng; Liang, Hanghua; Hou, Jianbin; Hu, Xiaosong; Wang, Feng; Zhang, Jiayi; Geng, Shengjun; Sun, Xiaochuan; Zhong, Dong; Cui, Hongjuan"

作者地址："[Peng, Wen; Liang, Hanghua; Hou, Jianbin; Hu, Xiaosong; Wang, Feng; Zhang, Jiayi; Geng, Shengjun; Cui, Hongjuan] Southwest Univ, State Key Lab Silkworm Genome Biol, Chongqing 400716, Peoples R China; [Peng, Wen; Liang, Hanghua; Hou, Jianbin; Hu, Xiaosong; Wang, Feng; Zhang, Jiayi; Geng, Shengjun; Cui, Hongjuan] Southwest Univ, Med Res Inst, Canc Ctr, Chongqing 400716, Peoples R China; [Shi, Shuang; Zhong, Jiacheng; Sun, Xiaochuan; Zhong, Dong] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing 400016, Peoples R China"

通信作者："Cui, HJ (通讯作者)，Southwest Univ, State Key Lab Silkworm Genome Biol, Chongqing 400716, Peoples R China.; Cui, HJ (通讯作者)，Southwest Univ, Med Res Inst, Canc Ctr, Chongqing 400716, Peoples R China.; Zhong, D (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing 400016, Peoples R China."

来源：ONCOGENE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000787474100005

JCR分区：Q1

影响因子：8

年份：2022

卷号：41

期号：22

开始页：3051

结束页：3063

文献类型：Article

关键词：　

摘要："CBX3, also known as HP1 gamma, is a major isoform of heterochromatin protein 1, whose deregulation has been reported to promote the development of human cancers. However, the molecular mechanism of CBX3 in glioblastoma multiforme (GBM) are unclear. Our study reported the identification of CBX3 as a potential therapeutic target for GBM. Briefly, we found that, CBX3 is significantly upregulated in GBM and reduces patient survival. In addition, functional assays demonstrated that CBX3 significantly promote the proliferation, invasion and tumorigenesis of GBM cells in vitro and in vivo. Mechanistically, Erlotinib, a small molecule targeting epidermal growth factor receptor (EGFR) tyrosine kinase, was used to demonstrate that CBX3 direct the malignant progression of GBM are EGFR dependent. Previous studies have shown that PARK2(Parkin) and STUB1(Carboxy Terminus of Hsp70-Interacting Protein) are EGFR-specific E3 ligases. Notably, we verified that CBX3 directly suppressed PARK2 and STUB1 at the transcriptional level through its CD domain to reduce the ubiquitination of EGFR. Moreover, the CSD domain of CBX3 interacted with PARK2 and regulated its ubiquitination to further reduce its protein level. Collectively, these results revealed an unknown mechanism underlying the pathogenesis of GBM and confirmed that CBX3 is a promising therapeutic target."

基金机构：Natural Science Foundation of Chongqing [cstc2019jcyj-zdxmX0033]; Chongqing Doctoral Research and Innovation Project [CYB21131]

基金资助正文：This research was supported by the Natural Science Foundation of Chongqing (cstc2019jcyj-zdxmX0033) and Chongqing Doctoral Research and Innovation Project (CYB21131).