Mechanistic Links Between Obesity, Insulin, and Cancer

Overview

Journal Trends Cancer

Publisher Cell Press

Specialty Oncology

Date 2020 Feb 17

PMID 32061306

Citations 38

Authors

Rachel J Perry

Gerald I Shulman

Affiliations

Soon will be listed here.

Abstract

Obesity and type 2 diabetes (T2D) increase the prevalence and worsen the prognosis of more than a dozen tumor types; however, the mechanism for this association remains hotly debated. Here we discuss a potential role for insulin as the key hormonal mediator of tumor metabolism and growth in obesity-associated insulin resistance.

Citing Articles

Chronic obesity does not alter cancer survival in mice.

Panzeri I, Madaj Z, Fagnocchi L, Apostle S, Tompkins M, Hostetter G bioRxiv. 2024; .

PMID: 39463991 PMC: 11507782. DOI: 10.1101/2024.10.14.618190.

Association of metabolic obesity phenotypes with risk of overall and site-specific cancers: a systematic review and meta-analysis of cohort studies.

Mahamat-Saleh Y, Aune D, Freisling H, Hardikar S, Jaafar R, Rinaldi S Br J Cancer. 2024; 131(9):1480-1495.

PMID: 39317703 PMC: 11519895. DOI: 10.1038/s41416-024-02857-7.

Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.

Engin A, Engin A Adv Exp Med Biol. 2024; 1460:727-766.

PMID: 39287871 DOI: 10.1007/978-3-031-63657-8_25.

Deciphering the role of immune system in the obesity-cancer relationship.

Bleriot C, Anagnostopoulos G, Ginhoux F Cell Res. 2024; 35(1):3-4.

PMID: 39079957 PMC: 11701093. DOI: 10.1038/s41422-024-01008-0.

Combined ultrasound endoscopy-guided fine-needle aspiration with DNA methylation of SHOX2 and RASSF1A genes to enhance the auxiliary diagnostic precision of pancreatic cancer.

Shan Y, Teng Y, Guan C, Mao Z, Lu C, Ding W Heliyon. 2024; 10(13):e34028.

PMID: 39071574 PMC: 11282983. DOI: 10.1016/j.heliyon.2024.e34028.

References

Saraei P, Asadi I, Azam Kakar M, Moradi-Kor N . The beneficial effects of metformin on cancer prevention and therapy: a comprehensive review of recent advances. Cancer Manag Res. 2019; 11:3295-3313. PMC: 6497052. DOI: 10.2147/CMAR.S200059. View

Ohkuma T, Peters S, Woodward M . Sex differences in the association between diabetes and cancer: a systematic review and meta-analysis of 121 cohorts including 20 million individuals and one million events. Diabetologia. 2018; 61(10):2140-2154. PMC: 6133170. DOI: 10.1007/s00125-018-4664-5. View

Morita M, Sato T, Nomura M, Sakamoto Y, Inoue Y, Tanaka R . PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth. Cancer Cell. 2018; 33(3):355-367.e7. DOI: 10.1016/j.ccell.2018.02.004. View

Idorn M, Straten P . Exercise and cancer: from "healthy" to "therapeutic"?. Cancer Immunol Immunother. 2017; 66(5):667-671. PMC: 5406418. DOI: 10.1007/s00262-017-1985-z. View

Wang Y, Nasiri A, Damsky W, Perry C, Zhang X, Rabin-Court A . Uncoupling Hepatic Oxidative Phosphorylation Reduces Tumor Growth in Two Murine Models of Colon Cancer. Cell Rep. 2018; 24(1):47-55. PMC: 6056247. DOI: 10.1016/j.celrep.2018.06.008. View

Carstensen B, Read S, Friis S, Sund R, Keskimaki I, Svensson A . Cancer incidence in persons with type 1 diabetes: a five-country study of 9,000 cancers in type 1 diabetic individuals. Diabetologia. 2016; 59(5):980-8. PMC: 4826427. DOI: 10.1007/s00125-016-3884-9. View

Avgerinos K, Spyrou N, Mantzoros C, Dalamaga M . Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism. 2018; 92:121-135. DOI: 10.1016/j.metabol.2018.11.001. View

Rabin-Court A, Rodrigues M, Zhang X, Perry R . Obesity-associated, but not obesity-independent, tumors respond to insulin by increasing mitochondrial glucose oxidation. PLoS One. 2019; 14(6):e0218126. PMC: 6561592. DOI: 10.1371/journal.pone.0218126. View

Hopkins B, Pauli C, Du X, Wang D, Li X, Wu D . Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature. 2018; 560(7719):499-503. PMC: 6197057. DOI: 10.1038/s41586-018-0343-4. View

10.

Hursting S, Berger N . Energy balance, host-related factors, and cancer progression. J Clin Oncol. 2010; 28(26):4058-65. PMC: 2982796. DOI: 10.1200/JCO.2010.27.9935. View

11.

Birks S, Peeters A, Backholer K, OBrien P, Brown W . A systematic review of the impact of weight loss on cancer incidence and mortality. Obes Rev. 2012; 13(10):868-91. DOI: 10.1111/j.1467-789X.2012.01010.x. View

12.

Guertin D, Sabatini D . Defining the role of mTOR in cancer. Cancer Cell. 2007; 12(1):9-22. DOI: 10.1016/j.ccr.2007.05.008. View

13.

Hundal R, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V . Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000; 49(12):2063-9. PMC: 2995498. DOI: 10.2337/diabetes.49.12.2063. View

14.

Iqbal M, Siddiqui F, Gupta V, Chattopadhyay S, Gopinath P, Kumar B . Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2. Mol Cancer. 2013; 12:72. PMC: 3710280. DOI: 10.1186/1476-4598-12-72. View

15.

Shulman G . Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014; 371(23):2237-8. DOI: 10.1056/NEJMc1412427. View