Cited by 247Metabolism, Diabetes, and CancerPancreatic and Hepatic Oncology ResearchPI3K/AKT/mTOR signaling in cancer

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Crosstalk between Insulin/Insulin-like Growth Factor-1 Receptors and G Protein-Coupled Receptor Signaling Systems: A Novel Target for the Antidiabetic Drug Metformin in Pancreatic Cancer

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Rozengurt, Enrique, Sinnett-Smith, James, Kisfalvi, Krisztina·2010·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-09-2229PMC PMC2862089

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Abstract

Insulin/insulin-like growth factor 1(IGF-1) receptors and G protein-coupled receptors (GPCR) signaling systems are implicated in autocrine-paracrine stimulation of a variety of malignancies, including ductal adenocarcinoma of the pancreas, one of the most lethal human diseases. Novel targets for pancreatic cancer therapy are urgently needed. We identified a crosstalk between insulin/IGF-1 receptors and GPCR signaling systems in pancreatic cancer cells, leading to enhanced signaling, DNA synthesis, and proliferation. Crosstalk between these signaling systems depends on mammalian target of rapamycin (mTOR) complex 1 (mTORC1). Metformin, the most widely used drug in the treatment of type 2 diabetes, activates AMP kinase (AMPK), which negatively regulates mTORC1. Recent results show that metformin-induced activation of AMPK disrupts crosstalk between insulin/IGF-1 receptor and GPCR signaling in pancreatic cancer cells and inhibits the growth of these cells in xenograft models. Given that insulin/IGF-1 and GPCRs are implicated in other malignancies, a similar crosstalk mechanism may be operative in other cancer cell types. Recent epidemiological studies linked administration of metformin with a reduced risk of pancreatic, breast, and prostate cancer in diabetic patients. We posit that crosstalk between insulin/IGF-1 receptor and GPCR signaling is a mechanism for promoting the development of certain types of cancer and a target for the prevention and therapy of these diseases via metformin administration. Clin Cancer Res; 16(9); 2505–11. ©2010 AACR.

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“또한 metformin은 insulin-like growth factor-1을 감소시키고 human epidermal growth factor receptor-2 신호를 억제함으로써 혈관 신생억제, 세포고사, 세포주기 정지 등을 유도하여 암을 억제 하기도 한다.(28-33) 최근 실험실 연구에서 metformin을 항암제”
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Authors: Rozengurt, E., Sinnett-Smith, J., & Kisfalvi, K.
Affiliations: University of California, Los Angeles (US)
Authors' Affiliation: Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles California
Corresponding author: Rozengurt, Enrique
ORCID: Rozengurt, Enrique
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2010-04-28
Volume: 16
Issue: 9
Pages: 2505-2511
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-09-2229
PMC: PMC2862089
OpenAlex: W2158170204
Cited by: 247
References: 64
Citations by year: 2026: 2 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 12 · 2021: 9 · 2020: 13 · 2019: 12 · 2018: 9 · 2017: 19 · 2016: 20 · 2015: 20 · 2014: 21 · 2013: 30 · 2012: 23
FWCI: 10.81
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R21CA137292)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK56930, P30 DK 41301, R0-1 DK55003, R01DK056930, P30DK041301, R01DK055003)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: metformin, G protein-coupled receptors, pancreatic cancer, mTORC1, AMPK, autocrine and paracrine signaling, cell proliferation, cancer prevention, drug repurposing
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Animals, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Metformin, Models, Biological, Pancreatic Neoplasms, Proteins, Receptor, Insulin, Transcription Factors, Signal Transduction, Receptor, IGF Type 1, Receptor Cross-Talk, Receptors, G-Protein-Coupled, Multiprotein Complexes, TOR Serine-Threonine Kinases

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Crosstalk between Insulin/Insulin-like Growth Factor-1 Receptors and G Protein-Coupled Receptor Signaling Systems: A Novel Target for the Antidiabetic Drug Metformin in Pancreatic Cancer

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