Genetic ablation of tumor necrosis factor-alpha attenuates the promoted colonic Wnt signaling in high fat diet-induced obese mice

Guo, Chi; Kim, Susan J.; Frederick, Armina-Lyn M.; Li, Jinchao; Jin, Yu; Zeng, Huawei; Mason, Joel B.; Liu, Zhenhua

doi:10.1016/j.jnutbio.2019.108302

Cited by 9 publications

(4 citation statements)

References 38 publications

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“…In accordance with previous studies demonstrating the role of hyperglycemia in carcinogenesis, a recent study has shown that hyperglycemia can induce the Wnt/β-catenin signaling pathway, promoting cancer cell survival and the progression of hyperglycemia-related cancer (57). Obesity has also been reported to activate the Wnt/βcatenin signaling pathway in a TNF-α-dependent way (58). Moreover, aberrant insulin/insulin-like growth factor-1 (IGF-1) signaling, which has a long-standing role in cancer, is activated by hyperglycemia or obesity and is believed to be an essential mediator of the oncogenic effects of these metabolic disorders (59).…”

Section: Cell Signaling Pathways Associated With Cancersupporting

confidence: 85%

The Role of Aberrant Metabolism in Cancer: Insights Into the Interplay Between Cell Metabolic Reprogramming, Metabolic Syndrome, and Cancer

Gong²,

2020

Front. Oncol.

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Metabolic syndrome (MetS) is characterized by hyperglycemia, hypertension, dyslipidemia and abdominal obesity. Patients with MetS or other metabolic disorders are more susceptible to cancer development and recurrence and have a worse long-term prognosis. Moreover, the metabolic reprogramming observed in cancer cells has also been described as one of the new hallmarks of cancer. Thus, aberrant metabolism has been proposed as an important risk factor for cancer. Chronic inflammation, reactive oxygen species (ROS), and oncogenic signaling pathways are considered as main potential triggers. Considering the strong association between metabolism and cancer, metabolism-modulating drugs, including metformin and statins, as well as adopting a healthy lifestyle, have been extensively investigated as strategies to combat cancer. Furthermore, strategies that interfere with the metabolic rewiring of cells may also have potent anti-cancer effects. In this article, we provide a comprehensive review of current knowledge on the relationship between aberrant metabolism and cancer and discuss the potential use of metabolism-targeting strategy for the treatment of cancer.

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Section: Cell Signaling Pathways Associated With Cancersupporting

confidence: 85%

The Role of Aberrant Metabolism in Cancer: Insights Into the Interplay Between Cell Metabolic Reprogramming, Metabolic Syndrome, and Cancer

Gong²,

2020

Front. Oncol.

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“…Wnt signaling is a key regulator of inflammatory signaling, which is conductive for tumorigenesis. 43 Diet-induced obesity produced colonic Tnf-α elevation and increased the risk of CRC via Wnt pathway, 43 PI3K-Akt and MAPK signaling pathways. 44 An obesity-associated gut microbiota reprograms the intestinal epigenome and leads to altered colonic gene expression.…”

Section: Discussionmentioning

confidence: 99%

Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice

Kang

Liu

et al. 2023

eBioMedicine

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“…In conclusion, an understanding of the mechanisms involved in the associations illustrated in Figures 1 and 2 will optimize the design of preventive and therapeutic strategies against cancer for individuals with high BMI. For example, it has been demonstrated that mice with diet-induced obesity exhibit increased tumorigenic Wnt signaling levels and that this effect is decreased by genetic suppression of the immune system through the ablation of tumor necrosis factor-alpha 25 . In this example, the knowledge of these complex interactions would influence the preventive and therapeutic approaches that target Wnt signaling.…”

Section: Discussionmentioning

confidence: 99%

Hypothesis: Mutations and Immunosurveillance in Obesity-Associated Colorectal Cancer

Lazarova¹,

Bordonaro²

2022

J. Cancer

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Tumorigenesis typically requires the accumulation of several driver gene mutations; therefore, there is a mutation threshold for the completion of the neoplastic process. Obesity increases the risk of cancer, and we have proposed that one mechanism whereby obesity raises the risk of microsatellite stable (MSS) colon cancer is by decreasing the mutation threshold. Therefore, obese MSS colon cancer patients should exhibit fewer driver gene mutations compared to normal body-mass index (BMI) patients. Our hypothesis is supported by results from analyses of The Cancer Genome Atlas (TCGA) data, which revealed that cancer genomes of obese MSS colon patients exhibit both fewer somatic mutations and fewer driver gene mutations. These findings could be explained by the high levels of obesity-associated cytokines and factors, the signaling pathways of which substitute for the additional driver gene mutations detected in normal-weight MSS colon cancer patients. Therefore, obesity-induced aberrant cell signaling might cooperate with initiating driver gene mutations to promote neoplastic development. Consistent with this possibility, we observed a lower number of KRAS mutations in high-BMI MSS colon cancer patients. This paper extends our hypothesis to address the interactions between obesity, immune surveillance in neoplastic development, and colorectal cancer (CRC) risk. A better understanding of these interactions will inform future preventive and therapeutic approaches against MSS CRC. We propose that the individual variations in the major histocompatibility class 1 (MHC-1) genotype interact with obesity to shape the tumor mutational landscape. Thus, the efficiency of the immune surveillance mechanisms to select against specific mutations may depend on both the MHC-1 genotype variant and the BMI of an individual. A high BMI is expected to reduce the number of driver gene mutations required to evade the MHC-1 surveillance mechanism and support an accelerated cancer progression.

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Genetic ablation of tumor necrosis factor-alpha attenuates the promoted colonic Wnt signaling in high fat diet-induced obese mice

Cited by 9 publications

References 38 publications

The Role of Aberrant Metabolism in Cancer: Insights Into the Interplay Between Cell Metabolic Reprogramming, Metabolic Syndrome, and Cancer

The Role of Aberrant Metabolism in Cancer: Insights Into the Interplay Between Cell Metabolic Reprogramming, Metabolic Syndrome, and Cancer

Altered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice

Hypothesis: Mutations and Immunosurveillance in Obesity-Associated Colorectal Cancer

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