14-3-3ɛ蛋白与肿瘤发生发展关系的研究进展

doi:10.13481/j.1671-587X.20240234

Abstract

Abstract:

14-3-3ε protein， also known as YWHAE protein， is a member of the 14-3-3 protein family characterized by a small relative molecular weight. Unlike protein kinases， 14-3-3ε protein does not participate in protein phosphorylation within the cells； instead， it forms the unique dimer structures and binds to the specific phosphorylated proteins，thereby regulating the activity and subcellular localization of the protein ligands and playing a role in the regulation of various cellular activities. The aberrant expression of 14-3-3ε protein has been discovered in the numerous cancers. The altered regulatory effect of aberrantly expressed 14-3-3ε protein on its protein ligands can affect the ligands’ subcellular localization and enzymatic activity， leading to the development， invasion， and metastasis of the tumor cells. The dimer structure of 14-3-3ε protein is a critical structural basis for its biological functions in the tumor progression， and disrupting the dimer structure could be targeted to kill the tumor cells. This review is based on the domestic and international research findings on the 14-3-3ε protein and covers its structure，mechanism， and the impact and mechanisms during the development process of gastric cancer， liver cancer， skin cancer， and various other tumors.

Key words: 14-3-3ε protein, Protein-protein interaction, Stomach neoplasm, Liver neoplasm, Epidermal neoplasm, Therapeutic target

CLC Number:

Haiyao PANG,Jun MENG. Research progress in relationship between 14-3-3ɛ protein and occurrence and development of tumor[J].Journal of Jilin University(Medicine Edition), 2024, 50(2): 572-578.

References 46

1	MOORE B， PEREZ V. Specific proteins of the nervous system ［J］. Physiological and Biochemical Aspects of Nervous Integration， 1967， 343-359
2	SEHNKE P C， ROSENQUIST M， ALSTERFJORD M， et al. Evolution and isoform specificity of plant 14-3-3 proteins［J］. Plant Mol Biol， 2002， 50（6）： 1011-1018.
3	JAUBERT S， LAFFAIRE J B， LEDGER T N， et al. Comparative analysis of two 14-3-3 homologues and their expression pattern in the root-knot nematode Meloidogyne incognita［J］. Int J Parasitol， 2004， 34（7）： 873-880.
4	CAU Y， VALENSIN D， MORI M， et al. Structure， function， involvement in diseases and targeting of 14-3-3 proteins： an update［J］. Curr Med Chem， 2018， 25（1）： 5-21.
5	LUK S C， GARCIA-BARCELO M， TSUI S K， et al. Assignment of the human 14-3-3 epsilon isoform （YWHAE） to human chromosome 17p13 by in situ hybridization［J］. Cytogenet Cell Genet， 1997， 78（2）： 105-106.
6	WANG W， SHAKES D C. Molecular evolution of the 14-3-3 protein family［J］. J Mol Evol， 1996， 43（4）： 384-398.
7	WU C Y， JAN Y J， KO B S， et al. Prognostic significance of 14-3-3ε， aldo-keto reductase family 1 B10 and metallothionein-1 in hepatocellular carcinoma［J］. Anticancer Res， 2018， 38（12）： 6855-6863.
8	AL-MATOUQ J， HOLMES T， HAMMILLER B，et al.Accumulation of cytoplasmic CDC25A in cutaneous squamous cell carcinoma leads to a dependency on CDC25A for cancer cell survival and tumor growth［J］. Cancer Lett， 2017， 410： 41-49.
9	ZHAO Y L， FANG X， FANG H， et al. ATPR-induced G0/G1 phase arrest in gastric cancer cells by regulating the binding of 14-3-3ε and filamin A［J］. Cancer Med， 2018， 7（7）： 3373-3384.
10	SLUCHANKO N N， GUSEV N B. Moonlighting chaperone-like activity of the universal regulatory 14-3-3 proteins［J］. FEBS J， 2017， 284（9）： 1279-1295.
11	GU Y M， JIN Y H， CHOI J K， et al. Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon［J］. FEBS Lett， 2006， 580（1）： 305-310.
12	SLUCHANKO N N， BUSTOS D M. Intrinsic disorder associated with 14-3-3 proteins and their partners［J］. Prog Mol Biol Transl Sci， 2019， 166： 19-61.
13	RITTINGER K， BUDMAN J， XU J， et al. Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding［J］. Mol Cell， 1999， 4（2）： 153-166.
14	YAFFE M B， RITTINGER K， VOLINIA S， et al. The structural basis for 14-3-3： phosphopeptide binding specificity［J］. Cell， 1997， 91（7）： 961-971.
15	BRIDGES D， MOORHEAD G B G. 14-3-3 proteins： a number of functions for a numbered protein［J］. Sci STKE， 2005， 2005（296）： re10.
16	OBSIL T， OBSILOVA V. Structural basis of 14-3-3 protein functions［J］. Semin Cell Dev Biol，2011，22（7）： 663-672.
17	LOPEZ-GIRONA A， FURNARI B， MONDESERT O，et al. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein［J］.Nature，1999，397（6715）： 172-175.
18	BRUNET A， KANAI F， STEHN J， et al. 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport［J］.J Cell Biol，2002，156（5）： 817-828.
19	ZIEGLER P， TELLER S， HA N H， et al. Phosphoproteomic identification of a PDX-1/14-3-3ε interaction in pancreatic beta cells［J］. Horm Metab Res， 2011， 43（3）： 165-170.
20	WACHI T， CORNELL B， TOYO-OKA K. Complete ablation of the 14-3-3epsilon protein results in multiple defects in neuropsychiatric behaviors［J］. Behav Brain Res， 2017， 319： 31-36.
21	TADESSE S， ANSHABO A T， PORTMAN N，et al. Targeting CDK2 in cancer： challenges and opportunities for therapy［J］.Drug Discov Today，2020，25（2）：406-413.
22	GONG X X， YAN L， GU H， et al. 14-3-3ε functions as an oncogene in SGC7901 gastric cancer cells through involvement of cyclin E and p27kip1［J］. Mol Med Rep， 2014， 10（6）： 3145-3150.
23	ZHANG X， ZENG B， WEN C， et al. YWHAE is a novel interaction partner of Helicobacter pylori CagA［J］. FEMS Microbiol Lett， 2018， 365（2）. DOI： 10.1093/femsle/fnx231 . doi: 10.1093/femsle/fnx231
24	YAN L， GU H， LI J， et al. RKIP and 14-3-3ε exert an opposite effect on human gastric cancer cells SGC7901 by regulating the ERK/MAPK pathway differently［J］. Dig Dis Sci， 2013， 58（2）： 389-396.
25	XIA Q， ZHAO Y L， WANG J L， et al. Proteomic analysis of cell cycle arrest and differentiation induction caused by ATPR， a derivative of all-trans retinoic acid， in human gastric cancer SGC-7901 cells［J］. Proteomics Clin Appl，2017，11（7/8）.DOI：10.1002/prca.201600099 . doi: 10.1002/prca.201600099
26	LEAL M F， RIBEIRO H F， REY J A， et al. YWHAE silencing induces cell proliferation， invasion and migration through the up-regulation of CDC25B and MYC in gastric cancer cells： new insights about YWHAE role in the tumor development and metastasis process［J］. Oncotarget， 2016， 7（51）： 85393-85410.
27	国家卫生健康委办公厅. 原发性肝癌诊疗指南（2022年版）［J］. 肿瘤综合治疗电子杂志， 2022， 8（2）： 16-53.
28	LIU T A， JAN Y J， KO B S， et al. 14-3-3ε overexpression contributes to epithelial-mesenchymal transition of hepatocellular carcinoma［J］. PLoS One， 2013， 8（3）： e57968.
29	LIU T A， JAN Y J， KO B S， et al. Correction： regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma［J］. Oncotarget， 2018， 9（79）： 35026.
30	WU Y J， KO B S， LIANG S M， et al. ZNF479 downregulates metallothionein-1 expression by regulating ASH2L and DNMT1 in hepatocellular carcinoma［J］. Cell Death Dis， 2019， 10（6）： 408.
31	KOHAMA Y， SAITO M， YADA M， et al. Regulation of the stability and activity of CDC25A and CDC25B by protein phosphatase PP2A and 14-3-3 binding［J］. Cell Signal， 2019， 54： 10-16.
32	HOLMES T R， AL-MATOUQ J， HOLMES M， et al. Targeting 14-3-3ε-CDC25A interactions to trigger apoptotic cell death in skin cancer［J］. Oncotarget， 2020， 11（35）： 3267-3278.
33	HOLMES T R， MATOUQ JAL， HOLMES M， et al. Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma［J］. Carcinogenesis， 2021， 42（2）： 232-242.
34	AL-MATOUQ J， HOLMES T R， HANSEN L A. CDC25B and CDC25C overexpression in nonmelanoma skin cancer suppresses cell death［J］. Mol Carcinog， 2019， 58（9）： 1691-1700.
35	ZHA J， HARADA H， YANG E， et al. Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X（L）［J］. Cell， 1996， 87（4）： 619-628.
36	NOMURA M， SHIMIZU S， SUGIYAMA T， et al. 14-3-3 interacts directly with and negatively regulates pro-apoptotic Bax［J］. J Biol Chem， 2015， 290（11）： 6753.
37	ZHAO J F， XU H Q， DUAN Z Q， et al. miR-31-5p regulates 14-3-3 ɛ to inhibit prostate cancer 22RV1 cell survival and proliferation via PI3K/AKT/bcl-2 signaling pathway［J］. Cancer Manag Res， 2020， 12： 6679-6694.
38	ANGELES A K， HECKMANN D， FLOSDORF N， et al. The ERG-regulated LINC00920 promotes prostate cancer cell survival via the 14-3-3ε-FOXO pathway［J］. Mol Cancer Res， 2020， 18（10）： 1545-1559.
39	LI X， WANG C X， WANG S， et al. YWHAE as an HE4 interacting protein can influence the malignant behaviour of ovarian cancer by regulating the PI3K/AKT and MAPK pathways［J］.Cancer Cell Int，2021，21（1）： 302.
40	LU K， RUI G， LIU F， et al. 14-3-3ε is a nuclear matrix protein， and its altered expression and localization are associated with curcumin-induced apoptosis of MG-63 cells［J］. Oncol Lett， 2018， 15（1）： 338-346.
41	YANG Y， SANG Z Y， MA J， et al. KRAS， YWHAE， SP1 and MSRA as biomarkers in endometrial cancer［J］. Transl Cancer Res， 2021， 10（3）： 1295-1312.
42	ZHONG Z M， CHEN X， QI X， et al. Adaptor protein LNK promotes anaplastic thyroid carcinoma cell growth via 14-3-3 ε/γ binding［J］. Cancer Cell Int， 2020， 20： 11.
43	XU Y， FULCINITI M， SAMUR M K， et al. YWHAE/14-3-3ε expression impacts the protein load， contributing to proteasome inhibitor sensitivity in multiple myeloma［J］. Blood， 2020， 136（4）： 468-479.
44	YAO W J， TONG S， TAN J， et al. NF45 promotes esophageal squamous carcinoma cell invasion by increasing Rac1 activity through 14-3-3ε protein［J］. Arch Biochem Biophys， 2019， 663： 101-108.
45	WOODCOCK J M， COOLEN C， GOODWIN K L，et al.Destabilisation of dimeric 14-3-3 proteins as a novel approach to anti-cancer therapeutics［J］. Oncotarget， 2015， 6（16）： 14522-14536.
46	JIN M， WU L N， CHEN S， et al. Arsenic trioxide enhances the chemotherapeutic efficiency of cisplatin in cholangiocarcinoma cells via inhibiting the 14-3-3ε- mediated survival mechanism［J］. Cell Death Discov， 2020， 6（1）： 92.

[1]	Huijuan SONG,Zhenhua XU,Dongning HE. Effect of apolipoprotein C1 expression on proliferation and apoptosis of human liver cancer HepG2 cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2024, 50(1): 128-135.
[2]	Yang YU,Dan TIAN,Donghe NI,Duo ZHANG. Network pharmacologry and molecular docking analysis based on mechanism of monk fruit in treatment of diabetic nephropathy [J]. Journal of Jilin University(Medicine Edition), 2024, 50(1): 161-167.
[3]	Yifei SUN,Dinuo LI,Yubin WANG. Inhibitory effect of curcumin on proliferation and invasion of gastric cancer MGC-803 cells by down-regulating PI3K/Akt/mTOR signaling pathway protein expression [J]. Journal of Jilin University(Medicine Edition), 2023, 49(2): 332-340.
[4]	Yun LIU,Linqi ZHU,Shihe SHAO. Effects of circular RNA hsa_circ_0009735 on epithelial mesenchymal transformation, cell cycle, and autophagy of gastric cancer cells [J]. Journal of Jilin University(Medicine Edition), 2022, 48(6): 1498-1509.
[5]	Xianshun XIE,Wei WANG,Haibing JIANG. Effect of miR-431-3p on proliferation and apoptosis of gastric cancer cells and its mechanism of targeted regulation of CTDP1 gene expression [J]. Journal of Jilin University(Medicine Edition), 2022, 48(6): 1555-1565.
[6]	Qian ZHANG,Jing LI. Inhibitory effect of TLR4 gene overexpression on autophagy of gastric cancer cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2022, 48(5): 1238-1246.
[7]	Guangsong XU,Haibing JIANG,Jing PAN,Guoqing LI. Inhibitory effects of betulinic acid on migration and invasion of gastric cancer MGC-803 cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2022, 48(1): 122-128.
[8]	Lili QIN,Xiaobo MA,Tianye ZHAO,Xuerong TAO,Min ZHENG,Xueying WANG,Jiaxin YI,Yanhua WU,Jing JIANG. Effects of MMP-9 and TIMP-1 expressions on prognostic evaluation of gastric cancer patients after radical gastrectomy [J]. Journal of Jilin University(Medicine Edition), 2022, 48(1): 163-171.
[9]	Runhong MU,Yijiu AI,Yupeng LI,Rui LIN,Siping YE,Fang MA,Xiao GUO. Expression of recombinant human IL-17A in gastric cancer tissue and its effects on proliferation, invasion, migration and apoptosis of gastric cancer BGC-823 cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(6): 1510-1517.
[10]	Tianyi WANG,Yufeng ZHU,Miao SUN,Wei WANG. Application of three-dimensional reconstruction combined with indocyanine green intraoperative navigation in diagnosis and treatment of liver cancer [J]. Journal of Jilin University(Medicine Edition), 2021, 47(4): 1014-1021.
[11]	Jie YANG,Wubin HE,Ni AN,Wencong KONG,Rongjian SU,Xuezhe WANG. Regulatory effect of glucose-regulating protein 78 on radiotherapy sensitivity of liver cancer cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(4): 888-895.
[12]	Runhong MU, Xinzhu LIU, Rui LIN, Yupeng LI, Luyao WANG, Chunyu WANG, Xiao GUO. Effect of PRDX6 over-expression of proliferation, invasion and migration of liver cancer cells and its molecular mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 559-565.
[13]	Nuan WANG,Lijuan YANG,Juanjuan DAI,Aili WANG,Yan WU,Chengxia LIU. Promotion effects of MARCH1 on migration and invasion of human gastric cancer cells through PI3K/AKT signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 352-359.
[14]	Haiying ZHANG,Wenxin ZHANG,Wenjing ZHAO,Wei LI. Induction effect of gallic acid on apoptosis of human hepatocellular carcinoma HepG-2 cells through regulating mitochondrial oxidative phosphorylation [J]. Journal of Jilin University(Medicine Edition), 2021, 47(1): 125-132.
[15]	Ruiying SUN,Yang LI,Xu ZHAO,Linlin QU,Wei XU,Yunli ZHANG. Detection of serum levels of gastric cancer-related cytokines and their clinical significances in diagnosis of gastric cancer [J]. Journal of Jilin University(Medicine Edition), 2020, 46(6): 1274-1282.

Research progress in relationship between 14-3-3ɛ protein and occurrence and development of tumor

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 46

Related Articles 15

Metrics

Comments

Recommended 0