ArticlePloS one2016
The Activation of ERK1/2 and JNK MAPK Signaling by Insulin/IGF-1 Is Responsible for the Development of Colon Cancer with Type 2 Diabetes Mellitus.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03813381 (The Impact of a Moderate CAlorie and Protein REstriction PROgram), which is not on this map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Impact of a Moderate CAlorie and Protein REstriction PROgram (CARE-PRO) as an Efficient and Affordable Therapeutic Strategy in Patients With Barrett's Esophagus.
Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- Temporal Trends in Colorectal Cancer Associated With Type 2 Diabetes Mellitus in U.S. Adults, 1999-2023: A CDC Wonder Database Analysis-A Population-Based Cross-Sectional Study.Health science reports · 2026Article
- The Role of Insulin Resistance in Cancer.Current oncology (Toronto, Ont.) · 2025Review
- Insulin‑like growth factor in cancer: New perspectives (Review).Molecular medicine reports · 2025Review
- Betulinic acid and obesity-related disorders.Frontiers in pharmacology · 2025Review
- Recent advances in the development and application of colorectal cancer mouse models.Frontiers in pharmacology · 2025Review
- Associations of diabetes and mortality among colorectal cancer patients from the Southern Community Cohort Study.British journal of cancer · 2024Article
- Unveiling the role of RAC3 in the growth and invasion of cisplatin-resistant bladder cancer cells.Journal of cellular and molecular medicine · 2024Article
- Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R.EMBO reports · 2022Article
- Pro-tumorigenic role of type 2 diabetes-induced cellular senescence in colorectal cancer.Frontiers in oncology · 2022Review
- Deep Learning Analysis of the Adipose Tissue and the Prediction of Prognosis in Colorectal Cancer.Frontiers in nutrition · 2022Article
- Insulin-like growth factor-1 improves postoperative cognitive dysfunction following splenectomy in aged rats.Experimental and therapeutic medicine · 2021Article
- Multitargeted Effects of Vitexin and Isovitexin on Diabetes Mellitus and Its Complications.TheScientificWorldJournal · 2021Review
- Mechanisms Underlying Hepatocellular Carcinoma Progression in Patients with Type 2 Diabetes.Journal of hepatocellular carcinoma · 2021Review
- Involvement of IGF/IGFBP/Erk axis in the exercise-mediated preventive effects on colorectal cancer in rats.International journal of clinical and experimental pathology · 2021Article
- Blood feeding activates the vitellogenic stage of oogenesis in the mosquito Aedes aegypti through inhibition of glycogen synthase kinase 3 by the insulin and TOR pathways.Developmental biology · 2019Article
- Clinical significance of serum IGFBP-3 in colorectal cancer.Journal of clinical laboratory analysis · 2019Article
- Molecular evidence of field cancerization initiated by diabetes in colon cancer patients.Molecular oncology · 2019Article
- Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways.Journal of experimental & clinical cancer research : CR · 2019Article
- Impact of Metabolic Syndrome Diagnosis and Its Treatment on Survival of Colorectal Cancer Patients.Journal of cancer epidemiology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies showed that type 2 diabetes mellitus (T2DM) is linked to increased risk of developing colon cancer. Insulin and insulin-like growth factor 1 (IGF-1) are increased in patients with T2DM. The increased insulin and IGF-1 may be responsible for the developing of colon cancer. In this study, we investigated the effects and mechanisms of insulin and IGF-1 in colon cancer development in vitro and in vivo. Insulin and IGF-1 alone or together elevated proliferation and reduced apoptosis in colon cancer MC38 cells. Meanwhile, insulin and IGF-1 promoted the phosphorylation of extracellular-signal regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Treatment with ERK1/2 or JNK inhibitor in the presence of insulin and IGF-1 significantly decreased B-cell lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) expression and finally increased apoptosis and inhibited the proliferation. Accelerative colon tumor growth was found in a mouse model of T2DM with db/db mice which got high level of endogenous insulin and IGF-1. Furthermore, the inhibition of ERK1/2 or JNK suppressed the development of colon tumor in vivo. These results suggest that the activation of ERK1/2 and JNK signaling by insulin and IGF-1, at least in part, is responsible for the development of colon cancer with T2DM.
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