|Table of Contents|

Molecular mechanism of exercise antitumor

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 22
Page:
4256-4261
Research Field:
Publishing date:

Info

Title:
Molecular mechanism of exercise antitumor
Author(s):
GUO Kaikai1XIE Hong2
1.Tianjin Key Laboratory of Exercise Physiology and Sports Medicine,Institute of Sport,Exercise & Health,Tianjin University of Sport,Tianjin 300381,China;2.School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China.
Keywords:
exercisetumormolecular mechanism
PACS:
R730.1
DOI:
10.3969/j.issn.1672-4992.2023.22.031
Abstract:
Exercise training has been shown to reduce the incidence of cancer and inhibit tumor growth.More and more research evidence shows that regular physical activity plays a good role in primary tumor prevention,prolonging the survival time of tumor patients,improving the quality of life and so on.By activating specific signal molecules and related pathways,exercise can not only regulate energy metabolism and maintain exercise,but also promote skeletal muscle to secrete cytokines and immune factors and recruit immune cells,in order to achieve the purpose of inhibiting the growth of tumor cells.The good benefit of exercise is the main way for the body to prevent cancer and combat tumor growth.As an adjuvant therapy,the benefit of exercise has been paid more and more attention by clinical researchers,and exercise often cooperates with specific drugs to treat cancer.In the progress of cancer prevention and anti-cancer through exercise,researchers have established a variety of cancer models with mice,and done a lot of researches on the molecular mechanism of cancer prevention and anti-cancer through exercise,and made some progress,but there is still a long way to go to reach the treatment plan of human beings.This paper briefly reviews the molecular mechanism of exercise against tumor.

References:

[1] HANNAH R SPAULDING,ZHEN YAN.AMPK and the adaptation to exercise[J].Annu Rev Physiol,2022,84:209-227.
[2] FENG LL,LI BW,XI Y,et al.Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction[J].Am J Physiol Cell Physiol,2022,322(2):C164-C176.
[3] JEREMY R PEARSON,NICOLE MOODIE,KEVAN W STOUT,et al.Similar responses in the Akt/protein kinase B signaling pathway following different lower-body exercise volumes in recreationally active men[J].J Strength Cond Res,2023,37(5):1034-1041.
[4] PARKER L EVANS,SHAWNA L MCMILLIN,LUKE A WEYRAU CH,et al.Regulation of skeletal muscle glucose transport and glucose metabolism by exercise training[J].Nutrients,2019,11(10):2432.
[5] JESSY CHEN,THOMAS FLEMING,SYLVIA KATZ,et al.CaM Kinase II-delta is required for diabetic hyperglycemia and retinopathy but not nephropathy[J].Diabetes,2021,70(2): 616-626.
[6]KATHRYN ANNE SKELDING,JOHN AP ROSTAS.Regulation of multifunctional Calcium/Calmodulin stimulated protein kinases by molecular targeting[J].Adv Exp Med Biol,2020,1131:649-679.
[7] JEFFREY RERICKSON,LAETITIA PEREIRA,LIANGUO WANG,et al.Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation[J].Nature,2013,502(7471):372-376.
[8] MARIYA KRONLAGE,MATTHIAS DEWENTER,JOHANNES GROSSO,et al.O-GlcNAcylation of histone deacetylase 4 protects the diabetic heart from failure[J].Circulation,2019,140(7): 580-594.
[9] JITCY S JOSEPH,KRISHNAN ANAND,SIBUSISO T MALINDISA,et al.Exercise,CaMKII,and type 2 diabetes[J].EXCLI J,2021,20:386-399.
[10]EDWARD O OJUKA,VEERAI GOYARAM,JAMES AH SMITH.The role of CaMKII in regulating GLUT4 expression in skeletal muscle[J].Am J Physiol Endocrinol Metab,2012,303(3): E322-E331.
[11]DAVID C WRIGHT,KATHLEEN A HUCKER,JOHN O HOLLOSZY,et al.Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions[J].Diabetes,2004,53(2):330-335.
[12] MELANIE H WONG,ALEXANDRA B SAMAL,MIKE LEE,et al.TheKN-93 molecule inhibits Calcium/Calmodulin-dependent protein kinase II (CaMKII) activity by binding to Ca(2+)/CaM[J].J Mol Biol,2019,431(7):1440-1459.
[13] EVA R CHIN.Role of Ca2+/calmodulin-dependent kinases in skeletal muscle plasticity[J].J Appl Physiol (1985),2005,99(2):414-423.
[14] GRAEME J GOWANS,D GRAHAME HARDIE.AMPK:a cellular energy sensor primarily regulated by AMP[J].Biochem Soc Trans,2014,42(1):71-75.
[15] GREG L MCKIE,DAVID C WRIGHT.Biochemical adaptations in white adipose tissue following aerobic exercise:from mitochondrial biogenesis to browning[J].Biochem J,2020,477(6):1061-1081.
[16]HIROYASU HATAKEYAMA,TAISUKE MORINO,TAKUYA ISH II,et al.Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities[J].J Biol Chem,2019,294(4):1161-1172.
[17] MAN MOHAN SHRESTHA,CHUN-YAN LIM,XUEZHI BI,et al.Tmod3 Phosphorylation Mediates AMPK-Dependent GLUT4 Plasma Membrane Insertion in Myoblasts[J].Front Endocrinol (Lausanne),2021,12:653557.
[18] HOLMES BF,KURTH-KRACZEK EJ,WINDER WW.Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4,hexokinase,and glycogen in muscle[J].J Appl Physiol (1985),1999,87(5):1990-1995.
[19] WINDER WW,HOLMES BF,RUBINK DS,et al.Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle[J].J Appl Physiol (1985),2000,88(6):2219-2226.
[20] HAYLEY M O' NEILL,JAMES S LALLY,SANDRA GALIC,et al.AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice[J].Diabetologia,2014,57(8):1693-1702.
[21] ZHIPING CHEN,TERRY J STEPHENS,SID MURTHY,et al.Effect of exercise intensity on skeletal muscle AMPK signaling in humans[J].Diabetes,2003,52(9):2205-2212.
[22] STEVEN C MOORE,I-MIN LEE,ELISABETE WEIDERPASS,et al.Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults[J].JAMA Intern Med,2016,176(6):816-825.
[23]NOELIA ZAGALAZ-ANULA,MARA JOS MORA-RUBIO,ESTEBAN OBRERO-GAITN,et al.Recreational physical activity reduces breast cancer recurrence in female survivors of breast cancer:A meta-analysis[J].Eur J Oncol Nurs,2022,59:102162.
[24] ROY J SHEPHARD.Physical activity and prostate cancer:An updated review[J].Sports Med,2017,47(6):1055-1073.
[25]ERIN L VAN BLARIGAN,CHARLES S FUCHS,DONNA NIEDZ WIECKI,et al.Association of survival with adherence to the American cancer society nutrition and physical activity guidelines for cancer survivors after colon cancer diagnosis:The CALGB 89803/Alliance trial[J].JAMA Oncol,2018,4(6):783-790.
[26] DANNA SHEINBOIM,SHIVANG PARIKH,PAULEE MANICH,et al.An Exercise-induced metabolic shield in distant organs blocks cancer progression and metastatic dissemination[J].Cancer Res,2022,82(22):4164-4178.
[27] IGOR L GOMES-SANTOS,ZOHREH AMOOZGAR,ASHWIN S KUMAR,et al.Exercise training improves tumor control by increasing CD8 T-cell infiltration via CXCR3 signaling and sensitizes breast cancer to immune checkpoint blockade[J].Cancer Immunol Res,2021,9(7):765-778.
[28] RICHARD S METCALFE,RACHAEL KEMP,SHANE M HEFFERNAN,et al.Anti-carcinogenic effects of exercise-conditioned human serum:evidence,relevance and opportunities[J].Eur J Appl Physiol,2021,121(8):2107-2124.
[29] LEE W JONES,MARILYN L KWAN,ERIN WELTZIEN,et al.Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer:The LACE and pathways studies[J].Cancer Res,2016,76(18):5415-5422.
[30] TEPPEI MORIKAWA,AYA KUCHIBA,MAI YAMAUCHI,et al.Association of CTNNB1 (beta-catenin) alterations,body mass index,and physical activity with survival in patients with colorectal cancer[J].JAMA,2011,305(16):1685-1694.
[31] LISA H COLBERT,KIM C WESTERLIND,SUSAN N PERKINS,et al. Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer[J].Medicine and Science in Sports and Exercise,2009,41(8):1597-1605.
[32] UBALDO E MARTINEZ-OUTSCHOORN,MARIA PEIRIS-PAG S,RICHARD G PESTELL,et al.Cancer metabolism:a therapeutic perspective[J].Nature Reviews Clinical Oncology,2017,14(2):113.
[33]JESPER FRANK CHRISTENSEN,CASPER SIMONSEN,PERNILLE HOJMAN.Exercise training in cancer control and treatment[J].Compr Physiol,2018,9(1):165-205.
[34]WANG QY,ZHOU WL.Roles and molecular mechanisms of physical exercise in cancer prevention and treatment[J].J Sport Health Sci,2021,10(2):201-210.
[35]LINDA A BUSS,GABI U DACHS.Voluntary exercise slows breast tumor establishment and reduces tumor hypoxia in ApoE(-/-) mice[J].J Appl Physiol (1985),2018,124(4):938-949.
[36] CAMILA S PADILHA,MAYRA T TESTA,POLIANA C MARINE LLO,et al.Resistance exercise counteracts tumor growth in two carcinoma rodent models[J].Med Sci Sports Exerc,2019,51(10):2003-2011.
[37] ANNE-CHRISTINE PIGUET,UTTARA SARAN,CEDRIC SIMILLION,et al.Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis[J].J Hepatol,2015,62(6): 1296-1303.
[38]MASAHIRO AOKI,TERUAKI FUJISHITA.Oncogenic roles of the PI3K/AKT/mTOR axis[J].Curr Top Microbiol Immunol,2017,407: 153-189.
[39] WANG Y,XU WB,YAN ZX,et al.Metformin induces autophagy and G0/G1 phase cell cycle arrest in myeloma by targeting the AMPK/mTORC1 and mTORC2 pathways[J].J Exp Clin Cancer Res,2018,37(1):63.
[40] BRANDON FAUBERT,GINO BOILY,SAID IZREIG,et al.AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo[J].Cell Metab,2013,17(1):113-124.
[41] RAKESH K JAIN. Normalization of tumor vasculature:an emerging concept in antiangiogenic therapy[J].Science,2005,307(5706):58-62.
[42] FAUSTINO-ROCHA AI,SILVA A,GABRIEL J,et al.Long-term exercise training as a modulator of mammary cancer vascularization[J].Biomed Pharmacother,2016,81:273-280.
[43] LEE W JONES,JODI ANTONELLI,ELIZABETH M MASKO,et al.Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer[J].J Appl Physiol (1985),2012,113(2):263-272.
[44] LEE W JONES,BENJAMIN L VIGLIANTI,JESSICA A TASHJIAN,et al.Effect of aerobic exercise on tumor physiology in an animal model of human breast cancer[J].J Appl Physiol (1985),2010,108(2):343-348.
[45] YANN S GALLOT,ANNE-C CILE DURIEUX,JOSIANE CASTELLS,et al.Myostatin gene inactivation prevents skeletal muscle wasting in cancer[J].Cancer Res,2014,74(24):7344-7356.
[46] SERKAN KIR,JAMES P WHITE,SANDRA KLEINER,et al.Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia[J].Nature,2014,513(7516):100-104.
[47] SERKAN KIR,HIROTAKA KOMABA,ANA P GARCIA,et al.PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer[J].Cell Metab,2016,23(2):315-323.
[48] THERESA MADER,THOMAS CHAILLOU,ESTELA SANTOS ALVES,et al.Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer[J].J Cachexia Sarcopenia Muscle,2022,13(2):1151-1163.
[49] PERNILLE HOJMAN,JONAS FJELBYE,BO ZERAHN,et al.Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice[J].PLoS One,2014,9(9):e109030.
[50] LINE PEDERSEN,MANJA IDORN,GITTE H OLOFSSON,et al.Voluntary running suppresses tumor growth through epinephrine-and IL-6-dependent NK cell mobilization and redistribution[J].Cell Metab,2016,23(3):554-562.
[51] CHRISTIANO R R ALVES,WILLIAN DAS NEVES,NEY R DE ALMEIDA,et al.Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/TRIP15/ALIEN[J].Mol Metab,2020,39:101012.
[52] LU LH,CHEN XF,LU P,et al.Analysis of the effect of exercise combined with diet intervention on postoperative quality of life of breast cancer patients[J].Comput Math Methods Med,2022,2022:4072832.
[53] REGULA FURRER,ANNA SE J JAUCH,TATA NAGESWARA RAO,et al.Remodeling of metabolism and inflammation by exercise ameliorates tumor-associated anemia[J].Sci Adv,2021,7(37):eabi4852.
[54] SHIRIN SADIGHPARVAR,SABER GHAZIZADEH DARBAND,BAHMAN YOUSEFI,et al.Combination of quercetin and exercise training attenuates depression in rats with 1,2-dimethylhydrazine-induced colorectal cancer:Possible involvement of inflammation and BDNF signalling[J].Exp Physiol,2020,105(9):1598-1609.
[55] LEANDRO Z AGUDELO,TERESA FEMENA,FUNDA ORHAN,et al.Skeletal muscle PGC-1alpha1 modulates kynurenine metabolism and mediates resilience to stress-induced depression[J].Cell,2014,159(1): 33-45.
[56]MAJA SCHLITTLER,MICHEL GOINY,LEANDRO Z AGUDELO,et al.Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans[J].Am J Physiol Cell Physiol,2016,310(10):C836-C840.
[57]MICHAEL GLEESON,NICOLETTE C BISHOP,DAVID J STENS EL,et al.The anti-inflammatory effects of exercise:mechanisms and implications for the prevention and treatment of disease[J].Nat Rev Immunol,2011,11(9):607-615.
[58] MICHAEL P GUSTAFSON,ARA CELI DICOSTANZO,COURTNEY M WHEATLEY,et al.A systems biology approach to investigating the influence of exercise and fitness on the composition of leukocytes in peripheral blood[J].J Immunother Cancer,2017,5:30.
[59] ALEXANDRA LEDO,DAVID SCHUB,CLEMENS ZILLER,et al.Elite athletes on regular training show more pronounced induction of vaccine-specific T-cells and antibodies after tetravalent influenza vaccination than controls[J].Brain Behav Immun,2020,83:135-145.
[60]MANJA IDORN,PERNILLE HOJMAN.Exercise-dependent regulation of NK cells in cancer protection[J].Trends Mol Med,2016,22(7):565-577.
[61] BENTE K PEDERSEN,MARK A FEBBRAIO.Muscles,exercise and obesity:skeletal muscle as a secretory organ[J].Nat Rev Endocrinol,2012,8(8):457-465.
[62] PERNILLE HOJMAN,CHRISTINE DETHLEFSEN,CLAUS BRA NDT,et al.Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth[J].Am J Physiol Endocrinol Metab,2011,301(3):E504-E510.
[63] PERNILLE HOJMAN,RIKKE STAGAARD,EMI ADACHI-FER NANDEZ,et al.Exercise suppresses tumor growth independent of high fat food intake and associated immune dysfunction[J].Sci Rep,2022,12(1):5476.
[64] HELENE RUNDQVIST,PEDRO VELI A,LAURA BARBIERI,et al.Cytotoxic T-cells mediate exercise-induced reductions in tumor growth[J].Elife,2020,9:e59996.
[65] BENTE K PEDERSEN,MARK A FEBBRAIO.Muscle as an endocrine organ:focus on muscle-derived interleukin-6[J].Physiol Rev,2008,88(4):1379-1406.
[66] DANIEL T FISHER,MICHELLE M APPENHEIMER,SHARON S EVANS.The two faces of IL-6 in the tumor microenvironment[J].Semin Immunol,2014,26(1):38-47.
[67] ANTOINE MAR AIS,JULIEN CHERFILS-VICINI,CHARLOTTE VIANT,et al.The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells[J].Nat Immunol,2014,15(8):749-757.
[68]NAOKO SATOH-TAKAYAMA,SARAH LESJEAN-POTTIER,PAULO VIEIRA,et al.IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors[J].J Exp Med,2010,207(2):273-280.
[69]KEVIN C CONLON,ENRICO LUGLI,HUGH C WELLES,et al.Redistribution,hyperproliferation,activation of natural killer cells and CD8 T cells,and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer[J].J Clin Oncol,2015,33(1):74-82.
[70] EMMA KURZ,CAROLINA ALCANTARA HIRSCH,TANNER D ALTON,et al.Exercise-induced engagement of the IL-15/IL-15Ralpha axis promotes anti-tumor immunity in pancreatic cancer[J].Cancer Cell,2022,40(7):720-737.e5.
[71] JIN-SOO KIM,REBEKAH L WILSON,DENNIS R TAAFFE,et al.Myokine expression and tumor-suppressive effect of serum after 12 wk of exercise in prostate cancer patients on ADT[J].Med Sci Sports Exerc,2022,54(2):197-205.

Memo

Memo:
National Natural Science Foundation of China(No.31971100);国家自然科学基金资助项目(编号:31971100)
Last Update: 1900-01-01