SHP2 mutations promote glycolysis and inhibit apoptosis via PKM2/hnRNPK signaling in colorectal cancer

doi:10.1016/j.isci.2024.110462

科研成果详情

题名	SHP2 mutations promote glycolysis and inhibit apoptosis via PKM2/hnRNPK signaling in colorectal cancer
作者	Zhou, Bo 1,2,3; Fan, Zhuoyang 1,2,3; He, Guodong 4,5; Zhang, Wei 1,2,3; Yang, Guowei 1,2,3; Ye, Lechi6; Xu, Jianmin 4,5; Liu, Rong 1,2,3
发表日期	2024-08-16
发表期刊	ISCIENCE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Cancer Molecular biology
其他关键词	NUCLEAR TRANSLOCATION ; DRUG-RESISTANCE ; PROGRESSION ; PKM2 ; PATHWAY ; HNRNPK ; GROWTH ; UBIQUITINATION ; METASTASIS ; MYC
摘要	Colorectal cancer (CRC) is one of the most common gastrointestinal tumors. Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) mutations occur in human solid tumors, including CRC. However, the function and underlying mechanism in CRC have not been well characterized. We demonstrated that the SHP2 D61Y and SHP2 E76K mutations occurred in CRC tissues, and these mutations promoted CRC cell proliferation, migration/invasion, and reduced CDDP-induced cell apoptosis in vitro and in vivo . Mechanistically, SHP2 D61Y and SHP2 E76K promote glycolysis by accelerating pyruvate kinase M2 (PKM2) nuclear translocation through mechanism beyond ERK activation. PKM2-IN-1 attenuates PKM2dependent glycolysis and reduce glucose uptake, lactate production, and ATP levels promoted by SHP2D 61Y and SHP2 E76K in CRC cells. Furthermore, PKM2 upregulates heterogeneous nuclear ribonucleoprotein K (hnRNPK) expression and increases CRC cell proliferation and migration/invasion via regulating hnRNPK ubiquitination. These findings provide evidence that SHP2 D61Y and SHP2 E76K regulate CDDPinduced apoptosis, glucose metabolism, and CRC migration/invasion through PKM2 nuclear translocation and PKM2/hnRNPK signaling.
资助项目	Shanghai Clinical Research Center for Interventional Medicine [19MC1910300]; Fudan Zhongshan Clinical Research Fund [ZSBY022]; Beijing Medical Award Fund Hengrui medical research programme [YXJL 2022-0972-1225]
出版者	CELL PRESS
ISSN	2589-0042
EISSN	2589-0042
卷号	27 期号:8
DOI	10.1016/j.isci.2024.110462
页数	22
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:001273735900001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39104405
SCOPUSEID	2-s2.0-85198519435
通讯作者地址	[Liu, Rong]Fudan Univ, Zhongshan Hosp, Dept Intervent Radiol, Shanghai 200032, Peoples R China. ; [Liu, Rong]Natl Clin Res Ctr Intervent Med, Shanghai 200032, Peoples R China. ; [Liu, Rong]Shanghai Inst Med Imaging, Shanghai 200032, Peoples R China. ; [Xu, Jianmin]Fudan Univ, Zhongshan Hosp, Dept Colorectal Surg, Shanghai 200032, Peoples R China. ; [Xu, Jianmin]Shanghai Engn Res Ctr Colorectal Canc Minimally In, Shanghai 200032, Peoples R China. ; [Ye, Lechi]Wenzhou Med Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, Wenzhou 325000, Peoples R China.
Scopus学科分类	Multidisciplinary
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/216727
专题	附属第一医院附属第一医院_肛肠外科
通讯作者	Ye, Lechi; Xu, Jianmin; Liu, Rong
作者单位	1.Fudan Univ, Zhongshan Hosp, Dept Intervent Radiol, Shanghai 200032, Peoples R China; 2.Natl Clin Res Ctr Intervent Med, Shanghai 200032, Peoples R China; 3.Shanghai Inst Med Imaging, Shanghai 200032, Peoples R China; 4.Fudan Univ, Zhongshan Hosp, Dept Colorectal Surg, Shanghai 200032, Peoples R China; 5.Shanghai Engn Res Ctr Colorectal Canc Minimally In, Shanghai 200032, Peoples R China; 6.Wenzhou Med Univ, Affiliated Hosp 1, Dept Colorectal & Anal Surg, Wenzhou 325000, Peoples R China
通讯作者单位	附属第一医院; 肛肠外科
推荐引用方式 GB/T 7714	Zhou, Bo,Fan, Zhuoyang,He, Guodong,et al. SHP2 mutations promote glycolysis and inhibit apoptosis via PKM2/hnRNPK signaling in colorectal cancer[J]. ISCIENCE,2024,27(8).
APA	Zhou, Bo., Fan, Zhuoyang., He, Guodong., Zhang, Wei., Yang, Guowei., ... & Liu, Rong. (2024). SHP2 mutations promote glycolysis and inhibit apoptosis via PKM2/hnRNPK signaling in colorectal cancer. ISCIENCE, 27(8).
MLA	Zhou, Bo,et al."SHP2 mutations promote glycolysis and inhibit apoptosis via PKM2/hnRNPK signaling in colorectal cancer".ISCIENCE 27.8(2024).