PFKFB4对胃癌细胞侵袭和迁移能力的影响及其作用

doi:10.11904/j.issn.1002-3070.2020.01.007

Abstract

Abstract: Objective The Objective of this study was to investigate whether kinase PFKFB4 was involved in the regulating invasion and migration of gastric cancer cells and its mechanism of action.Methods The SRC family proteins interacting with PFKFB4 were detected by immunoprecipitation.The downstream regulatory genes were identified by transcriptome sequencing.The relationship between downstream genes and phosphorylated SRC proteins was verified by Western blot and qRT-PCR.The effect of PFKFB4 related to pathway on abilities of migration and invasion was detected in gastric cancer cells by Transwell assay.Results PFKFB4 could interact with SRC-2.The expression of SRC-2 was not affected by PFKFB4.But PFKFB4 could phosphorylate serine at site 698 of SRC-2.After phosphorylation of SRC-2 Ser698,downstream regulatory gene-LKB1 at levels of mRNA and protein was down-regulated.As a result,the migration and invasion ability of gastric cancer cells was enhanced.Conclusion PFKFB4 negatively regulates the expression of tumor suppressor gene-LKB1 by phosphorylation of SRC-2,and enhances the migration and invasion of gastric cancer cells.

Key words: PFKFB4, Phosphorylation, SRC-2, Gastric cancer cells, Invasion, Migration

CLC Number:

R735.2

WANG Ming, SUN Tiye. Effects of PFKFB4 on invasion and migration of gastric cancer cells and its mechanism[J]. Journal of Practical Oncology, 2020, 34(1): 37-42.

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References

1 裘法祖.外科学[M]第3版.北京:人民卫生出版社,1995:83.
2 Ferlay J,Soerjomataram I,Dikshit R,et al.Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J].Int J Cancer,2015,136(5):359-386.
3 Chesney J,Clark J,Klarer AC,et al.Fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4(PFKFB4)is required for the glycolytic response to hypoxia and tumor growth[J].Oncotarget,2014,5(16):6670-6686.
4 Dasgupta S,Rajapakshe K,Zhu B,et al.Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer[J].Nature,2018,556(7700):249-254.
5 Minchenko OH,Tsuchihara K,Minchenko DO,et al.Mechanisms of regulation of PFKFB expression in pancreatic and gastric cancer cells[J].World J Gastroenterol,2014,20(38):13705-13717.
6 Cai M,Liang X,Sun X,et al.Nuclear receptor coactivator 2 promotes human breast cancer cell growth by positively regulating the MAPK/ERK pathway[J].Front Oncol,2019,9:164.
7 Jana D,Yurii C,Megan K,et al.Glucocorticoid-dependent phosphorylation of the transcriptional coregulator GRIP1[J].Mol Cell Biol,2011,32(4):730-739.
8 Dasgupta S,Putluri N,Long W,et al.Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis[J].J Clin Invest,2015,125(3):1174-1188.
9 Dobrovolna J,Chinenov Y,Kennedy MA,et al.Glucocorticoid-dependent phosphorylation of the transcriptional coregulator GRIP1[J].Mol Cell Biol,2012,32(4):730-739.
10 Sakata J,Abe Y,Uyeda K.Molecular cloning of the DNA and expression and characterization of rat testes fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase[J].J Biol Chem,1991,266(24):15764-15770.
11 Shang M,Su B,Lipke EA,et al.Spermatogonial stem cells specific marker identification in channel catfish,Ictalurus punctatus and blue catfish,I.furcatus[J].Fish Physiol Biochem,2015,41(6):1545-1556.
12 Chesney J,Clark J,Lanceta L,et al.Targeting the sugar metabolism of tumors with a first-in-class 6-phosphofructo-2-kinase(PFKFB4)inhibitor[J].Oncotarget,2015,6(20):18001-18011.
13 Shen L,Du J,Xia Y,et al.Genome-wide landscape of DNA methylomes and their relationship with mRNA and miRNA transcriptomes in oxidative and glycolytic skeletal muscles[J].Sci Rep,2016,6:32186-32197.
14 Onate SA,Tsai SY,Tsai MJ,et al.Sequence and characterization of a coactivator for the steroid hormone receptor superfamily[J].Science,1995,270(5240):1354-1357.
15 Lonard DM,O′Malley BW.Molecular pathways:targeting steroid receptor coactivators in cancer[J].Clin Cancer Res,2016,22(22):5403-5407.
16 He Z,Zhang J,Du Q,et al.SRC3 is a cofactor for RORgammat in Th17 differentiation but not thymocyte development[J].J Immunol,2019,202(3):760-769.
17 Wang L,Lonard DM,O′Malley BW.The role of steroid receptor coactivators in hormone dependent cancers and their potential as therapeutic targets[J].Horm Cancer,2016,7(4):229-235.
18 Browne AL,Charmsaz S,Vareslija D,et al.Network analysis of SRC-1 reveals a novel transcription factor hub which regulates endocrine resistant breast cancer[J].Oncogene,2018,37(15):2008-2021.
19 Fleet T,Stashi E,Zhu B.Genetic and environmental models of circadian disruption link SRC-2 function to hepatic pathology[J].J Biol Rhythms,2016,31(5):443-460.
20 Suresh S,Durakoglugil D,Zhou X,et al.SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer[J].PLoS Genet,2017,13(3):e1006650.
21 Chen W,Lu X,Chen Y,et al.Steroid receptor coactivator 3 contributes to host defense against enteric bacteria by recruiting neutrophils via upregulation of CXCL2 expression[J].J Immunol,2017,198(4):1606-1615.
22 Yuan Y,Shan N,Tan B,et al.SRC-3 plays a critical role in human umbilical vein endothelial cells by regulating the PI3K/Akt/mTOR pathway in preeclampsia[J].Reprod Sci,2018,25(5):748-758.
23 Torchia J,Rose DW,Inostroza J,et al.The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function[J].Nature,1997,387(6634):677-684.
24 Li S,Shang Y.Regulation of SRC family coactivators by post-translational modifications[J].Cell Signal,2007,19(6):1101-1112.
25 姚强,王宽,薛英威.SRC1在胃癌中的表达及其与预后的关系[J].实用肿瘤学杂志,2018,32(2):97-102.
26 Rohira AD,Yan F,Wang L,et al.Targeting SRC coactivators blocks the tumor-initiating capacity of cancer stem-like cells[J].Cancer Res,2017,77(16):4293-4304.
27 Reineke EL,Benham A,Soibam B,et al.Steroid receptor coactivator-2 is a dual regulator of cardiac transcription factor function[J].J Biol Chem,2014,289(25):17721-17735.
28 Suh JH,Lai L,Nam D,et al.Steroid receptor coactivator-2(SRC-2)coordinates cardiomyocyte paracrine signaling to promote pressure overload-induced angiogenesis[J].J Biol Chem,2017,292(52):21643-21652.
29 Madsen A,Bozickovic O,Bjune JI,et al.Metformin inhibits hepatocellular glucose,lipid and cholesterol biosynthetic pathways by transcriptionally suppressing steroid receptor coactivator 2(SRC-2)[J].Sci Rep,2015,5:16430-16442.
30 Szwarc MM,Kommagani R,Lessey BA,et al.The p160/steroid receptor coactivator family:potent arbiters of uterine physiology and dysfunction[J].Biol Reprod,2014,91(5):122-133.
31 Reineke EL,York B,Stashi E,et al.SRC-2 coactivator deficiency decreases functional reserve in response to pressure overload of mouse heart[J].PLoS One,2012,7(12):e53395.
32 Taylor BS,Schultz N,Hieronymus H,et al.Integrative genomic profiling of human prostate cancer[J].Cancer Cell,2010,18(1):11-22.
33 Foley C,Mitsiades N.Moving beyond the androgen receptor(AR):targeting AR-interacting proteins to treat prostate cancer[J].Horm Cancer,2016,7(2):84-103.
34 Li J,Liu J,Li P,et al.Loss of LKB1 disrupts breast epithelial cell polarity and promotes breast cancer metastasis and invasion[J].J Exp Clin Cancer Res,2014,33:70.

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Effects of PFKFB4 on invasion and migration of gastric cancer cells and its mechanism

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