Home LiteratureArticle Details
PMID: 27903152 Published · ppublish English Journal Article Review Research Support, N.I.H., Extramural

Obesity and Cancer Mechanisms: Cancer Metabolism.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology ·Vol. 34 ·No. 35 ·2016-00-10 ·Pages 4277-4283

Hopkins BD, Goncalves MD, Cantley LC

Abstract

Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. The positive energy balance linked with obesity induces a variety of systemic changes including altered levels of insulin, insulin-like growth factor-1, leptin, adiponectin, steroid hormones, and cytokines. Each of these factors alters the nutritional milieu and has the potential to create an environment that favors tumor initiation and progression. Although the complete ramifications of obesity as it relates to cancer are still unclear, there is convincing evidence that reducing the magnitude of the systemic hormonal and inflammatory changes has significant clinical benefits. This review will examine the changes that occur in the obese state and review the biologic mechanisms that connect these changes to increased cancer risk. Understanding the metabolic changes that occur in obese individuals may also help to elucidate more effective treatment options for these patients when they develop cancer. Moving forward, targeted clinical trials examining the effects of behavioral modifications such as reduced carbohydrate intake, caloric restriction, structured exercise, and/or pharmacologic interventions such as the use of metformin, in obese populations may help to reduce their cancer risk.

MeSH Terms
Biomarkers, Tumor/metabolism Disease Progression Energy Metabolism Humans Neoplasms/complications,metabolism Obesity/complications,metabolism Prognosis Risk Factors Signal Transduction Tumor Microenvironment
Chemicals
Biomarkers, Tumor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hopkins Benjamin D
All authors: Meyer Cancer Center, Weill Cornell Medical College, New York, NY.
Goncalves Marcus D
All authors: Meyer Cancer Center, Weill Cornell Medical College, New York, NY.
Cantley Lewis C
All authors: Meyer Cancer Center, Weill Cornell Medical College, New York, NY.
References (128)
128 references, click to expand
  1. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells.
    Mol Cell Biol. 1999 May;19(5):3278-88 PMID: 10207053
  2. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  3. Cellular mechanisms of insulin resistance.
    J Clin Invest. 2000 Jul;106(2):171-6 PMID: 10903330
  4. Mechanisms of energy restriction: effects of corticosterone on cell growth, cell cycle machinery, and apoptosis.
    Cancer Res. 2002 Sep 15;62(18):5280-7 PMID: 12234997
  5. The role of the IGF system in cancer: from basic to clinical studies and clinical applications.
    Oncology. 2002;63(4):317-32 PMID: 12417786
  6. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review.
    Cancer Epidemiol Biomarkers Prev. 2002 Dec;11(12):1531-43 PMID: 12496040
  7. Loss of IGF2 imprinting: a potential marker of colorectal cancer risk.
    Science. 2003 Mar 14;299(5613):1753-5 PMID: 12637750
  8. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults.
    N Engl J Med. 2003 Apr 24;348(17):1625-38 PMID: 12711737
  9. Prostate cancer cell-adipocyte interaction: leptin mediates androgen-independent prostate cancer cell proliferation through c-Jun NH2-terminal kinase.
    J Biol Chem. 2003 Oct 24;278(43):42660-7 PMID: 12902351
  10. IGF-I, IGF binding protein-3 and breast cancer risk: comparison of 3 meta-analyses.
    Int J Cancer. 2005 Jul 20;115(6):1006-7; author reply 1008 PMID: 15723358
  11. Obesity and cortisol status.
    Horm Metab Res. 2005 Apr;37(4):193-7 PMID: 15952076
  12. Leptin and cancer.
    J Cell Physiol. 2006 Apr;207(1):12-22 PMID: 16110483
  13. Adipocytokines and cancer.
    Physiol Res. 2006;55(3):233-44 PMID: 16238454
  14. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer.
    Eur J Cancer. 2005 Dec;41(18):2887-95 PMID: 16243513
  15. Adiponectin as a growth inhibitor in prostate cancer cells.
    Biochem Biophys Res Commun. 2006 Feb 24;340(4):1158-66 PMID: 16403434
  16. Estrogen carcinogenesis in breast cancer.
    N Engl J Med. 2006 Jan 19;354(3):270-82 PMID: 16421368
  17. Interleukin-6 production induced by leptin treatment promotes cell proliferation in an Apc (Min/+) colon epithelial cell line.
    Carcinogenesis. 2006 Jul;27(7):1507-15 PMID: 16597643
  18. The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis.
    Eur J Paediatr Neurol. 2006 May;10(3):148-51 PMID: 16632392
  19. Exercise for overweight or obesity.
    Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003817 PMID: 17054187
  20. A high-fat, ketogenic diet induces a unique metabolic state in mice.
    Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1724-39 PMID: 17299079
  21. leptin-induced growth stimulation of breast cancer cells involves recruitment of histone acetyltransferases and mediator complex to CYCLIN D1 promoter via activation of Stat3.
    J Biol Chem. 2007 May 4;282(18):13316-25 PMID: 17344214
  22. Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 concentrations and prostate cancer risk: results from the European Prospective Investigation into Cancer and Nutrition.
    Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1121-7 PMID: 17548673
  23. Quantitative mass spectrometry identifies insulin signaling targets in C. elegans.
    Science. 2007 Aug 3;317(5838):660-3 PMID: 17673661
  24. Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95 2.
    Endocr Relat Cancer. 2007 Sep;14(3):713-20 PMID: 17914101
  25. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study.
    BMJ. 2007 Dec 1;335(7630):1134 PMID: 17986716
  26. Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases.
    Endocr Relat Cancer. 2007 Dec;14(4):979-93 PMID: 18045950
  27. Effects of adiponectin on breast cancer cell growth and signaling.
    Br J Cancer. 2008 Jan 29;98(2):370-9 PMID: 18182989
  28. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial.
    Lancet Neurol. 2008 Jun;7(6):500-6 PMID: 18456557
  29. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity.
    Mol Syst Biol. 2008;4:214 PMID: 18682704
  30. Cancer cell metabolism: Warburg and beyond.
    Cell. 2008 Sep 5;134(5):703-7 PMID: 18775299
  31. Insulin and insulin-like growth factor signalling in neoplasia.
    Nat Rev Cancer. 2008 Dec;8(12):915-28 PMID: 19029956
  32. Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breast cancer subtypes and is related to poor survival.
    Cancer Res. 2008 Dec 15;68(24):10238-46 PMID: 19074892
  33. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women.
    J Natl Cancer Inst. 2009 Jan 7;101(1):48-60 PMID: 19116382
  34. Tumours with PI3K activation are resistant to dietary restriction.
    Nature. 2009 Apr 9;458(7239):725-31 PMID: 19279572
  35. Minireview: Obesity and breast cancer: the estrogen connection.
    Endocrinology. 2009 Jun;150(6):2537-42 PMID: 19372199
  36. Expression of insulin-like growth factor 2 in mesenchymal neoplasms.
    Mod Pathol. 2009 Jul;22(7):914-21 PMID: 19407853
  37. Understanding the Warburg effect: the metabolic requirements of cell proliferation.
    Science. 2009 May 22;324(5930):1029-33 PMID: 19460998
  38. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes.
    Diabetes Care. 2009 Sep;32(9):1620-5 PMID: 19564453
  39. Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer.
    Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18351-6 PMID: 19805051
  40. Circulating levels of insulin-like growth factor-II/mannose-6-phosphate receptor in obesity and type 2 diabetes.
    Growth Horm IGF Res. 2010 Jun;20(3):185-91 PMID: 20110184
  41. Androgens and obesity.
    Curr Opin Endocrinol Diabetes Obes. 2010 Jun;17(3):224-32 PMID: 20418719
  42. Interaction between adiponectin and leptin influences the risk of colorectal adenoma.
    Cancer Res. 2010 Jul 1;70(13):5430-7 PMID: 20516125
  43. Insulin signaling meets mitochondria in metabolism.
    Trends Endocrinol Metab. 2010 Oct;21(10):589-98 PMID: 20638297
  44. Discovery of canagliflozin, a novel C-glucoside with thiophene ring, as sodium-dependent glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus.
    J Med Chem. 2010 Sep 9;53(17):6355-60 PMID: 20690635
  45. Energy balance, host-related factors, and cancer progression.
    J Clin Oncol. 2010 Sep 10;28(26):4058-65 PMID: 20697088
  46. Metformin and other biguanides in oncology: advancing the research agenda.
    Cancer Prev Res (Phila). 2010 Sep;3(9):1060-5 PMID: 20810670
  47. Chemoprevention meets glucose control.
    Cancer Prev Res (Phila). 2010 Sep;3(9):1049-52 PMID: 20810671
  48. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants.
    Lancet. 2011 Feb 12;377(9765):557-67 PMID: 21295846
  49. Energy balance modulates colon tumor growth: Interactive roles of insulin and estrogen.
    Mol Carcinog. 2011 May;50(5):370-82 PMID: 21480390
  50. The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation.
    Trends Biochem Sci. 2011 Jun;36(6):320-8 PMID: 21531565
  51. Minireview: IGF, Insulin, and Cancer.
    Endocrinology. 2011 Jul;152(7):2546-51 PMID: 21540285
  52. Activation of phosphatidylinositol 3-kinase by insulin.
    Proc Natl Acad Sci U S A. 1990 Feb;87(4):1411-5 PMID: 2154747
  53. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial.
    Breast Cancer Res Treat. 2011 Aug;128(3):783-94 PMID: 21655990
  54. Does intentional weight loss reduce cancer risk?
    Diabetes Obes Metab. 2011 Dec;13(12):1063-72 PMID: 21733057
  55. Androgen receptor signaling in prostate cancer development and progression.
    J Carcinog. 2011;10:20 PMID: 21886458
  56. Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia.
    Oncogene. 2012 Jul 5;31(27):3213-22 PMID: 22037215
  57. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth.
    Nat Med. 2011 Oct 30;17(11):1498-503 PMID: 22037646
  58. Altered expression of insulin receptor isoforms in breast cancer.
    PLoS One. 2011;6(10):e26177 PMID: 22046260
  59. Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II.
    PLoS One. 2011;6(11):e27488 PMID: 22140443
  60. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors.
    J Clin Oncol. 2012 Jan 20;30(3):282-90 PMID: 22162589
  61. Hyperinsulinemia enhances c-Myc-mediated mammary tumor development and advances metastatic progression to the lung in a mouse model of type 2 diabetes.
    Breast Cancer Res. 2012 Jan 07;14(1):R8 PMID: 22226054
  62. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010.
    JAMA. 2012 Feb 1;307(5):491-7 PMID: 22253363
  63. The insulin and insulin-like growth factor receptor family in neoplasia: an update.
    Nat Rev Cancer. 2012 Feb 16;12(3):159-69 PMID: 22337149
  64. Elevated insulin receptor content in human breast cancer.
    J Clin Invest. 1990 Nov;86(5):1503-10 PMID: 2243127
  65. Stromal estrogen receptor-α promotes tumor growth by normalizing an increased angiogenesis.
    Cancer Res. 2012 Jun 15;72(12):3010-9 PMID: 22523036
  66. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial.
    J Clin Oncol. 2012 Jul 20;30(21):2593-600 PMID: 22564993
  67. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients.
    Nutrition. 2012 Oct;28(10):1028-35 PMID: 22840388
  68. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.
    PLoS One. 2012;7(7):e41992 PMID: 22848683
  69. Metformin in early breast cancer: a prospective window of opportunity neoadjuvant study.
    Breast Cancer Res Treat. 2012 Oct;135(3):821-30 PMID: 22933030
  70. Obesity, energy balance, and cancer: new opportunities for prevention.
    Cancer Prev Res (Phila). 2012 Nov;5(11):1260-72 PMID: 23034147
  71. Dietary sugars and body weight: systematic review and meta-analyses of randomised controlled trials and cohort studies.
    BMJ. 2012 Jan 15;346:e7492 PMID: 23321486
  72. Adipose tissue and adipocytes support tumorigenesis and metastasis.
    Biochim Biophys Acta. 2013 Oct;1831(10):1533-41 PMID: 23500888
  73. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.
    J Clin Oncol. 2013 Apr 20;31(12):1539-47 PMID: 23530101
  74. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.
    Eur J Clin Nutr. 2013 Aug;67(8):789-96 PMID: 23801097
  75. Autophagy is required for mitochondrial function, lipid metabolism, growth, and fate of KRAS(G12D)-driven lung tumors.
    Autophagy. 2013 Oct;9(10):1636-8 PMID: 23959381
  76. IGF2 and cancer.
    Endocr Relat Cancer. 2013 Oct 24;20(6):R321-39 PMID: 24080445
  77. Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer.
    Curr Opin Support Palliat Care. 2013 Dec;7(4):383-9 PMID: 24189893
  78. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors.
    Breast Cancer Res. 2013 Nov 19;15(6):R110 PMID: 24252402
  79. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme.
    J Neurooncol. 2014 Mar;117(1):125-31 PMID: 24442482
  80. Prevalence of childhood and adult obesity in the United States, 2011-2012.
    JAMA. 2014 Feb 26;311(8):806-14 PMID: 24570244
  81. Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower epithelial-mesenchymal transition signature and longer survival in squamous cell lung carcinoma.
    BMC Cancer. 2014 Feb 26;14:131 PMID: 24571613
  82. Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.
    Cancer Invest. 2014 May;32(4):150-7 PMID: 24605899
  83. SGLT inhibitors in management of diabetes.
    Lancet Diabetes Endocrinol. 2013 Oct;1(2):140-51 PMID: 24622320
  84. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.
    Int J Oncol. 2014 Jun;44(6):1843-52 PMID: 24728273
  85. Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer.
    Cancer Prev Res (Phila). 2014 Jul;7(7):748-57 PMID: 24819876
  86. Anti-diabetic doses of metformin decrease proliferation markers in tumors of patients with endometrial cancer.
    Gynecol Oncol. 2014 Sep;134(3):607-14 PMID: 24972190
  87. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer.
    Mol Cancer Ther. 2014 Oct;13(10):2361-71 PMID: 25122071
  88. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults.
    Lancet. 2014 Aug 30;384(9945):755-65 PMID: 25129328
  89. Metformin and gynecologic cancers.
    Obstet Gynecol Surv. 2014 Aug;69(8):477-89 PMID: 25144611
  90. Phase I study of intermittent oral dosing of the insulin-like growth factor-1 and insulin receptors inhibitor OSI-906 in patients with advanced solid tumors.
    Clin Cancer Res. 2015 Feb 15;21(4):693-700 PMID: 25208878
  91. Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett's esophagus.
    Clin Gastroenterol Hepatol. 2015 Apr;13(4):665-72.e1-4 PMID: 25218668
  92. Metformin and erlotinib synergize to inhibit basal breast cancer.
    Oncotarget. 2014 Nov 15;5(21):10503-17 PMID: 25361177
  93. Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer.
    Cancer Med. 2015 Feb;4(2):161-73 PMID: 25417601
  94. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors.
    Clin Cancer Res. 2015 Feb 15;21(4):730-8 PMID: 25500057
  95. Metformin and trametinib have synergistic effects on cell viability and tumor growth in NRAS mutant cancer.
    Oncotarget. 2015 Jan 20;6(2):969-78 PMID: 25504439
  96. Evidence for biological effects of metformin in operable breast cancer: biomarker analysis in a pre-operative window of opportunity randomized trial.
    Breast Cancer Res Treat. 2015 Feb;150(1):149-55 PMID: 25682077
  97. Highly specific role of the insulin receptor in breast cancer progression.
    Endocr Relat Cancer. 2015 Apr;22(2):145-57 PMID: 25694511
  98. Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32.
    J Natl Cancer Inst. 2015 Mar 04;107(3):null PMID: 25740979
  99. Multidrug and toxin extrusion 1 and human organic cation transporter 1 polymorphisms in patients with castration-resistant prostate cancer receiving metformin (SAKK 08/09).
    Prostate Cancer Prostatic Dis. 2015 Jun;18(2):167-72 PMID: 25753371
  100. Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study.
    Breast Cancer Res. 2015 Mar 03;17:32 PMID: 25849721
  101. The role of protein in weight loss and maintenance.
    Am J Clin Nutr. 2015 Apr 29;101(6):1320S-1329S PMID: 25926512
  102. Leptin activation of mTOR pathway in intestinal epithelial cell triggers lipid droplet formation, cytokine production and increased cell proliferation.
    Cell Cycle. 2015;14(16):2667-76 PMID: 26017929
  103. Metformin in patients with advanced pancreatic cancer: a double-blind, randomised, placebo-controlled phase 2 trial.
    Lancet Oncol. 2015 Jul;16(7):839-47 PMID: 26067687
  104. Mitochondrial free fatty acid β-oxidation supports oxidative phosphorylation and proliferation in cancer cells.
    Int J Biochem Cell Biol. 2015 Aug;65:209-21 PMID: 26073129
  105. Hyperinsulinemia, insulin resistance and colorectal adenomas: A meta-analysis.
    Metabolism. 2015 Oct;64(10):1324-33 PMID: 26169471
  106. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.
    Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2056-65 PMID: 26170063
  107. Effect of Metformin on Breast Ductal Carcinoma In Situ Proliferation in a Randomized Presurgical Trial.
    Cancer Prev Res (Phila). 2015 Oct;8(10):888-94 PMID: 26276754
  108. Phase II trial of metformin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas.
    Ecancermedicalscience. 2015 Aug 11;9:563 PMID: 26316884
  109. Metformin: risk-benefit profile with a focus on cancer.
    Expert Opin Drug Saf. 2015 Oct;14(10):1573-85 PMID: 26359221
  110. Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade.
    Clin Cancer Res. 2015 Oct 1;21(19):4270-7 PMID: 26429980
  111. (Ir)relevance of Metformin Treatment in Patients with Metastatic Pancreatic Cancer: An Open-Label, Randomized Phase II Trial.
    Clin Cancer Res. 2016 Mar 1;22(5):1076-85 PMID: 26459175
  112. Mechanisms linking obesity to altered metabolism in mice colon carcinogenesis.
    Oncotarget. 2015 Nov 10;6(35):38195-209 PMID: 26472027
  113. Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis.
    Eur J Cancer. 2015 Dec;51(18):2747-58 PMID: 26597445
  114. Sarcopenia and cachexia in the era of obesity: clinical and nutritional impact.
    Proc Nutr Soc. 2016 May;75(2):188-98 PMID: 26743210
  115. Measuring the biological effect of presurgical metformin treatment in endometrial cancer.
    Br J Cancer. 2016 Feb 2;114(3):281-9 PMID: 26794276
  116. Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy.
    Radiother Oncol. 2016 Mar;118(3):453-9 PMID: 26861738
  117. Metformin for chemoprevention of metachronous colorectal adenoma or polyps in post-polypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial.
    Lancet Oncol. 2016 Apr;17(4):475-483 PMID: 26947328
  118. Differential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma.
    J Clin Endocrinol Metab. 2016 Jul;101(7):2883-91 PMID: 27088794
  119. Phase 2 Trial of Metformin Combined With 5-Fluorouracil in Patients With Refractory Metastatic Colorectal Cancer.
    Clin Colorectal Cancer. 2016 Dec;15(4):321-328.e1 PMID: 27262895
  120. Proteomic modulation in breast tumors after metformin exposure: results from a "window of opportunity" trial.
    Clin Transl Oncol. 2017 Feb;19(2):180-188 PMID: 27305912
  121. Proceedings: Causes of death in cancer patients.
    Cancer. 1974 Feb;33(2):568-73 PMID: 4591273
  122. The insulin signaling system.
    J Biol Chem. 1994 Jan 7;269(1):1-4 PMID: 8276779
  123. An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.
    Cell. 1993 Apr 9;73(1):169-77 PMID: 8462097
  124. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling.
    Nature. 1993 May 6;363(6424):85-8 PMID: 8479541
  125. Role of genomic imprinting in Wilms' tumour and overgrowth disorders.
    Med Pediatr Oncol. 1996 Nov;27(5):470-5 PMID: 8827076
  126. Insulin receptor expression and clinical outcome in node-negative breast cancer.
    Proc Assoc Am Physicians. 1997 Nov;109(6):565-71 PMID: 9394418
  127. Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study.
    J Natl Cancer Inst. 1998 Jun 17;90(12):911-5 PMID: 9637140
  128. Leptin and the regulation of body weight in mammals.
    Nature. 1998 Oct 22;395(6704):763-70 PMID: 9796811
Article Info
Journal
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Abbr.
J Clin Oncol
ISSN
1527-7755
DOI
10.1200/JCO.2016.67.9712
Published
2016-00-10
Epub
2016-00-07
Pages
4277-4283
Language
English
Region
United States
NLM ID
8309333
PMCID
PMC5562429
Subset
IM
Grants
NCI NIH HHS · P01 CA120964 · United States
NIGMS NIH HHS · R01 GM041890 · United States
NCI NIH HHS · R35 CA197588 · United States
External Links
PubMed source DOI: 10.1200/JCO.2016.67.9712 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2