Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment

Agudelo, 2014, Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression, Cell, 159, 33, 10.1016/j.cell.2014.07.051 Angelin, 2017, Foxp3 reprograms T cell metabolism to function in low-glucose, high-lactate environments, Cell Metab., 25, 1282, 10.1016/j.cmet.2016.12.018 Aoi, 2013, A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise, Gut, 62, 882, 10.1136/gutjnl-2011-300776 Arsenis, 2017, Physical activity and telomere length: impact of aging and potential mechanisms of action, Oncotarget, 8, 45008, 10.18632/oncotarget.16726 Ashcraft, 2016, Efficacy and mechanisms of aerobic exercise on cancer initiation, progression, and metastasis: a critical systematic review of in vivo preclinical data, Cancer Res., 76, 4032, 10.1158/0008-5472.CAN-16-0887 Atherton, 2005, Selective activation of AMPK-PGC-1alpha or PKB-TSC2-mTOR signaling can explain specific adaptive responses to endurance or resistance training-like electrical muscle stimulation, FASEB J., 19, 786, 10.1096/fj.04-2179fje Aveseh, 2015, Exercise-induced changes in tumour LDH-B and MCT1 expression are modulated by oestrogen-related receptor alpha in breast cancer-bearing BALB/c mice, J. Physiol., 593, 2635, 10.1113/JP270463 Ballard-Barbash, 2012, Physical activity, biomarkers, and disease outcomes in cancer survivors: a systematic review, J. Natl. Cancer Inst., 104, 815, 10.1093/jnci/djs207 Benatti, 2015, Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation, Nat. Rev. Rheumatol., 11, 86, 10.1038/nrrheum.2014.193 Betof, 2015, Modulation of murine breast tumor vascularity, hypoxia and chemotherapeutic response by exercise, J. Natl. Cancer Inst., 107, djv040, 10.1093/jnci/djv040 Caruso, 2017, Depressive spectrum disorders in cancer: prevalence, risk factors and screening for depression: a critical review, Acta Oncol., 56, 146, 10.1080/0284186X.2016.1266090 Cavalheri, 2017, Preoperative exercise training for patients with non-small cell lung cancer, Cochrane Database Syst. Rev., 6, CD012020 Chen, 2017, Improving radiotherapy in cancer treatment: Promises and challenges, Oncotarget, 8, 62742, 10.18632/oncotarget.18409 Chen, 2006, Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism, Nat. Immunol., 7, 1299, 10.1038/ni1406 Christensen, 2014, Muscle dysfunction in cancer patients, Ann. Oncol., 25, 947, 10.1093/annonc/mdt551 Colbert, 2009, Exercise effects on tumorigenesis in a p53-deficient mouse model of breast cancer, Med. Sci. Sports Exerc., 41, 1597, 10.1249/MSS.0b013e31819f1f05 Conlon, 2015, 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. Clin. Oncol., 33, 74, 10.1200/JCO.2014.57.3329 Cooney, 2013, Exercise for depression, Cochrane Database Syst. Rev., 9, CD004366 De Palma, 2017, Microenvironmental regulation of tumour angiogenesis, Nat. Rev. Cancer, 17, 457, 10.1038/nrc.2017.51 DeBerardinis, 2008, The biology of cancer: metabolic reprogramming fuels cell growth and proliferation, Cell Metab., 7, 11, 10.1016/j.cmet.2007.10.002 Demark-Wahnefried, 2012, Weight management and its role in breast cancer rehabilitation, Cancer, 118, 2277, 10.1002/cncr.27466 Dethlefsen, 2016, Exercise regulates breast cancer cell viability: systemic training adaptations versus acute exercise responses, Breast Cancer Res. Treat., 159, 469, 10.1007/s10549-016-3970-1 Dethlefsen, 2017, Exercise-induced catecholamines activate the hippo tumor suppressor pathway to reduce risks of breast cancer development, Cancer Res., 77, 4894, 10.1158/0008-5472.CAN-16-3125 Dethlefsen, 2017, Every exercise bout matters: linking systemic exercise responses to breast cancer control, Breast Cancer Res. Treat., 162, 399, 10.1007/s10549-017-4129-4 Evans, 2015, Impact of acute intermittent exercise on natural killer cells in breast cancer survivors, Integr. Cancer Ther., 14, 436, 10.1177/1534735415580681 Evans, 2015, Fever and the thermal regulation of immunity: the immune system feels the heat, Nat. Rev. Immunol., 15, 335, 10.1038/nri3843 Fearon, 2013, Understanding the mechanisms and treatment options in cancer cachexia, Nat. Rev. Clin. Oncol., 10, 90, 10.1038/nrclinonc.2012.209 Ferrone, 2010, Dual roles for immunity in gastrointestinal cancers, J. Clin. Oncol., 28, 4045, 10.1200/JCO.2010.27.9992 Fischer, 2007, Inhibitory effect of tumor cell-derived lactic acid on human T cells, Blood, 109, 3812, 10.1182/blood-2006-07-035972 Fisher, 2011, IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells, J. Clin. Invest., 121, 3846, 10.1172/JCI44952 Friedenreich, 2016, Inflammatory marker changes in postmenopausal women after a year-long exercise intervention comparing high versus moderate volumes, Cancer Prev. Res. (Phila.), 9, 196, 10.1158/1940-6207.CAPR-15-0284 Gabriel, 2017, The limits of exercise physiology: from performance to health, Cell Metab., 25, 1000, 10.1016/j.cmet.2017.04.018 Gabriel, 2016, The Hippo signal transduction network for exercise physiologists, J. Appl. Physiol., 120, 1105, 10.1152/japplphysiol.01076.2015 Gallot, 2014, Myostatin gene inactivation prevents skeletal muscle wasting in cancer, Cancer Res., 74, 7344, 10.1158/0008-5472.CAN-14-0057 Galvão, 2010, Combined resistance and aerobic exercise program reverses muscle loss in men undergoing androgen suppression therapy for prostate cancer without bone metastases: a randomized controlled trial, J. Clin. Oncol., 28, 340, 10.1200/JCO.2009.23.2488 Gannon, 2015, Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro, Int. J. Cancer, 136, E197, 10.1002/ijc.29142 Gao, 2016, Local hyperthermia in head and neck cancer: mechanism, application and advance, Oncotarget, 7, 57367, 10.18632/oncotarget.10350 Garcia, 2016, Blood flow responses to mild-intensity exercise in ectopic vs. orthotopic prostate tumors; dependence upon host tissue hemodynamics and vascular reactivity, J. Appl. Physiol., 121, 15, 10.1152/japplphysiol.00266.2016 González-Alonso, 2012, Human thermoregulation and the cardiovascular system, Exp. Physiol., 97, 340, 10.1113/expphysiol.2011.058701 Gross, 2013, Cancer immunosurveillance and immunoediting by natural killer cells, Cancer J., 19, 483, 10.1097/PPO.0000000000000005 Hawley, 2014, Integrative biology of exercise, Cell, 159, 738, 10.1016/j.cell.2014.10.029 Henningsen, 2010, Dynamics of the skeletal muscle secretome during myoblast differentiation, Mol. Cell. Proteomics, 9, 2482, 10.1074/mcp.M110.002113 Hersey, 2009, Metabolic approaches to treatment of melanoma, Clin. Cancer Res., 15, 6490, 10.1158/1078-0432.CCR-09-0251 Higgins, 2014, Exercise-induced lung cancer regression: mechanistic findings from a mouse model, Cancer, 120, 3302, 10.1002/cncr.28878 Hojman, 2011, Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth, Am. J. Physiol. Endocrinol. Metab., 301, E504, 10.1152/ajpendo.00520.2010 Hojman, 2014, Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice, PLoS One, 9, e109030, 10.1371/journal.pone.0109030 Holmes, 2005, Physical activity and survival after breast cancer diagnosis, JAMA, 293, 2479, 10.1001/jama.293.20.2479 Horowitz, 2015, Exploiting the critical perioperative period to improve long-term cancer outcomes, Nat. Rev. Clin. Oncol., 12, 213, 10.1038/nrclinonc.2014.224 Hvid, 2013, Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy, Endocr. Relat. Cancer, 20, 621, 10.1530/ERC-12-0393 Idorn, 2016, Exercise-dependent regulation of NK cells in cancer protection, Trends Mol. Med., 22, 565, 10.1016/j.molmed.2016.05.007 Imayama, 2012, Effects of a caloric restriction weight loss diet and exercise on inflammatory biomarkers in overweight/obese postmenopausal women: a randomized controlled trial, Cancer Res., 72, 2314, 10.1158/0008-5472.CAN-11-3092 Jiang, 2013, Effects of limiting energy availability via diet and physical activity on mammalian target of rapamycin-related signaling in rat mammary carcinomas, Carcinogenesis, 34, 378, 10.1093/carcin/bgs350 Jones, 2013, Effect of exercise on markers of inflammation in breast cancer survivors: the Yale exercise and survivorship study, Cancer Prev. Res. (Phila.), 6, 109, 10.1158/1940-6207.CAPR-12-0278 Jones, 2016, Exercise and prognosis on the basis of clinicopathologic and molecular features in early-stage breast cancer: the LACE and pathways studies, Cancer Res., 76, 5415, 10.1158/0008-5472.CAN-15-3307 Kenfield, 2011, Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study, J. Clin. Oncol., 29, 726, 10.1200/JCO.2010.31.5226 Kim, 2015, Inflammation-induced activation of the indoleamine 2,3-dioxygenase pathway: relevance to cancer-related fatigue, Cancer, 121, 2129, 10.1002/cncr.29302 Kir, 2014, Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia, Nature, 513, 100, 10.1038/nature13528 Kir, 2016, PTH/PTHrP receptor mediates cachexia in models of kidney failure and cancer, Cell Metab., 23, 315, 10.1016/j.cmet.2015.11.003 Klil-Drori, 2017, Cancer, obesity, diabetes, and antidiabetic drugs: is the fog clearing?, Nat. Rev. Clin. Oncol., 14, 85, 10.1038/nrclinonc.2016.120 Kurgan, 2017, Inhibition of human lung cancer cell proliferation and survival by post-exercise serum is associated with the inhibition of Akt, mTOR, p70 S6K, and Erk1/2, Cancers (Basel), 9, E46, 10.3390/cancers9050046 Lee, 2010, Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index, Cancer Res., 70, 1564, 10.1158/0008-5472.CAN-09-3228 Lin, 2017, Breast cancer oral anti-cancer medication adherence: a systematic review of psychosocial motivators and barriers, Breast Cancer Res. Treat., 165, 247, 10.1007/s10549-017-4317-2 Lu, 2006, Stimulatory effect of voluntary exercise or fat removal (partial lipectomy) on apoptosis in the skin of UVB light-irradiated mice, Proc. Natl. Acad. Sci. USA, 103, 16301, 10.1073/pnas.0607789103 Marçais, 2014, The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells, Nat. Immunol., 15, 749, 10.1038/ni.2936 Martinez-Outschoorn, 2017, Cancer metabolism: a therapeutic perspective, Nat. Rev. Clin. Oncol., 14, 11, 10.1038/nrclinonc.2016.60 McCullough, 2013, Effects of exercise training on tumor hypoxia and vascular function in the rodent preclinical orthotopic prostate cancer model, J. Appl. Physiol., 115, 1846, 10.1152/japplphysiol.00949.2013 McCullough, 2014, Modulation of blood flow, hypoxia, and vascular function in orthotopic prostate tumors during exercise, J. Natl. Cancer Inst., 106, dju036, 10.1093/jnci/dju036 McTiernan, 2008, Mechanisms linking physical activity with cancer, Nat. Rev. Cancer, 8, 205, 10.1038/nrc2325 Meyerhardt, 2006, Physical activity and survival after colorectal cancer diagnosis, J. Clin. Oncol., 24, 3527, 10.1200/JCO.2006.06.0855 Mishra, 2012, Exercise interventions on health-related quality of life for cancer survivors, Cochrane Database Syst. Rev., 8, CD007566 Mishra, 2012, Exercise interventions on health-related quality of life for people with cancer during active treatment, Cochrane Database Syst. Rev. Mitsuishi, 2012, Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming, Cancer Cell, 22, 66, 10.1016/j.ccr.2012.05.016 Moore, 2016, Association of leisure-time physical activity with risk of 26 types of cancer in 1.44 million adults, JAMA Intern. Med., 176, 816, 10.1001/jamainternmed.2016.1548 Morikawa, 2011, Association of CTNNB1 (beta-catenin) alterations, body mass index, and physical activity with survival in patients with colorectal cancer, JAMA, 305, 1685, 10.1001/jama.2011.513 Müller, 2017, Type I interferons and natural killer cell regulation in cancer, Front. Immunol., 8, 304, 10.3389/fimmu.2017.00304 Nair, 2012, Autophagy and cardiovascular aging: lesson learned from rapamycin, Cell Cycle, 11, 2092, 10.4161/cc.20317 Nelson, 2008, The impact of T-cell immunity on ovarian cancer outcomes, Immunol. Rev., 222, 101, 10.1111/j.1600-065X.2008.00614.x Neufer, 2015, Understanding the cellular and molecular mechanisms of physical activity-induced health benefits, Cell Metab., 22, 4, 10.1016/j.cmet.2015.05.011 Newby, 2015, Interventions that may reduce depressive symptoms among prostate cancer patients: a systematic review and meta-analysis, Psychooncology, 24, 1686, 10.1002/pon.3781 Nilsen, 2016, Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy, Scand. J. Med. Sci. Sports, 26, 1026, 10.1111/sms.12543 Pagès, 2010, Immune infiltration in human tumors: a prognostic factor that should not be ignored, Oncogene, 29, 1093, 10.1038/onc.2009.416 Park, 2014, Obesity and cancer--mechanisms underlying tumour progression and recurrence, Nat. Rev. Endocrinol., 10, 455, 10.1038/nrendo.2014.94 Pedersen, 2008, Muscle as an endocrine organ: focus on muscle-derived interleukin-6, Physiol. Rev., 88, 1379, 10.1152/physrev.90100.2007 Pedersen, 2012, Muscles, exercise and obesity: skeletal muscle as a secretory organ, Nat. Rev. Endocrinol., 8, 457, 10.1038/nrendo.2012.49 Pedersen, 2015, Exercise as medicine - evidence for prescribing exercise as therapy in 26 different chronic diseases, Scand. J. Med. Sci. Sports, 25, 1, 10.1111/sms.12581 Pedersen, 2015, Effects of exercise on tumor physiology and metabolism, Cancer J., 21, 111, 10.1097/PPO.0000000000000096 Pedersen, 2016, Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution, Cell Metab., 23, 554, 10.1016/j.cmet.2016.01.011 Piguet, 2015, Regular exercise decreases liver tumors development in hepatocyte-specific PTEN-deficient mice independently of steatosis, J. Hepatol., 62, 1296, 10.1016/j.jhep.2015.01.017 Rundqvist, 2013, Effect of acute exercise on prostate cancer cell growth, PLoS One, 8, e67579, 10.1371/journal.pone.0067579 Sasso, 2015, A framework for prescription in exercise-oncology research, J. Cachexia Sarcopenia Muscle, 6, 115, 10.1002/jcsm.12042 Satoh-Takayama, 2010, IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors, J. Exp. Med., 207, 273, 10.1084/jem.20092029 Schadler, 2016, Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy, Oncotarget, 7, 65429, 10.18632/oncotarget.11748 Schiaffino, 2013, Mechanisms regulating skeletal muscle growth and atrophy, FEBS J., 280, 4294, 10.1111/febs.12253 Schlittler, 2016, Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans, Am. J. Physiol. Cell Physiol., 310, C836, 10.1152/ajpcell.00053.2016 Schmitz, 2010, American College of Sports Medicine roundtable on exercise guidelines for cancer survivors, Med. Sci. Sports Exerc., 42, 1409, 10.1249/MSS.0b013e3181e0c112 Schneider, 2017, Tissue-specific tumorigenesis: context matters, Nat. Rev. Cancer, 17, 239, 10.1038/nrc.2017.5 Sharma, 2015, Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential, Cell, 161, 205, 10.1016/j.cell.2015.03.030 Singh, 2013, A systematic review of pre-surgical exercise intervention studies with cancer patients, Surg. Oncol., 22, 92, 10.1016/j.suronc.2013.01.004 Strauss, 2010, Transmission of donor melanoma by organ transplantation, Lancet Oncol., 11, 790, 10.1016/S1470-2045(10)70024-3 Tarrado-Castellarnau, 2016, Oncogenic regulation of tumor metabolic reprogramming, Oncotarget, 7, 62726, 10.18632/oncotarget.10911 Tasdemir, 2016, BRD4 connects enhancer remodeling to senescence immune surveillance, Cancer Discov., 6, 612, 10.1158/2159-8290.CD-16-0217 Theriau, 2016, Voluntary physical activity abolishes the proliferative tumor growth microenvironment created by adipose tissue in animals fed a high fat diet, J. Appl. Physiol., 121, 139, 10.1152/japplphysiol.00862.2015 Thompson, 2009, Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis, IUBMB Life, 61, 895, 10.1002/iub.233 Tremblay, 2014, The Hippo transducer YAP1 transforms activated satellite cells and is a potent effector of embryonal rhabdomyosarcoma formation, Cancer Cell, 26, 273, 10.1016/j.ccr.2014.05.029 van Gemert, 2017, Association between changes in fat distribution and biomarkers for breast cancer, Endocr. Relat. Cancer, 24, 297, 10.1530/ERC-16-0490 Wall, 2017, Exercise improves V˙O2max and body composition in androgen deprivation therapy-treated prostate cancer patients, Med. Sci. Sports Exerc., 49, 1503, 10.1249/MSS.0000000000001277 Whitham, 2016, The ever-expanding myokinome: discovery challenges and therapeutic implications, Nat. Rev. Drug Discov., 15, 719, 10.1038/nrd.2016.153 Yu, 2012, Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling, Cell, 150, 780, 10.1016/j.cell.2012.06.037 Zanconato, 2016, YAP/TAZ at the roots of cancer, Cancer Cell, 29, 783, 10.1016/j.ccell.2016.05.005