The Role of Irisin in Cancer Disease

Pinkowska, Agnieszka; Podhorska‐Okołów, Marzenna; Dzięgiel, Piotr; Nowińska, Katarzyna

doi:10.3390/cells10061479

Cited by 27 publications

(34 citation statements)

References 76 publications

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“…Irisin is released as a result of post-translational modifications of the FNDC5 prohormone, encoded by the FNDC5 gene. The peptide composed of 112 amino acids is the result of cleavage and glycosylation of the extracellular domain of the prohormone [ 11 , 12 ]. FNDC5 is an N-glycan with two potential glycosylation sites (Asn36 and Asn81) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx

et al. 2021

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Background: Current studies indicate irisin role in carcinogenesis. The aim of the study was to investigate the expression of irisin in LSCCs and to determine its association with clinicopathological factors, as well as recognized markers of proliferation, i.e., Ki-67 and MCM3,5,7 and MT-I/II proteins. Material and methods: The research material consisted of 140 cases of LSCCs, 57 cases of laryngeal papillomas (BLs) and 14 controls (benign hypertrophic changes). Tissue microarrays were used to perform IHC. Western blot and immunofluorescence were performed in laryngeal cancer cell lines and normal keratinocytes. Results: Irisin expression levels were significantly increased in LSCC compared to BLs (p < 0.0001) and controls (p = 0.001). We noted a positive moderate and weak correlation between irisin and Ki-67, MCM3 and MT-I/II. We observed an elevated level of irisin expression with increasing tumor size (T1–2 vs. T3–4; p = 0.0348). The levels of irisin were higher in N0 than in N1 and N2–3 (p = 0.0031 and p = 0.0457, respectively). Our in vitro study revealed a higher level of irisin in Larynx Epidermoid Carcinoma 2 (HEp-2) cells compared to the control Normal Human Keratinocyte (HaCat) cell line. Conclusions: Increased irisin expression levels in LSCC and its correlation with clinicopathological and proliferation factors may indicate the potential role of irisin as a biomarker in the diagnostic process of LSCC.

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Section: Introductionmentioning

confidence: 99%

Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx

et al. 2021

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“…Recent studies have revealed that FNDC5 protects cells from oxidative damage in myocardial inflammation and neurological diseases ( 20 , 21 ) and reduces the production of ROS, inhibiting the occurrence of ferroptosis in cells ( 22 ). As the role of FNDC5 has also been gradually revealed in tumors ( 23 , 24 ) and in the progression of HCC, FNDC5 has been suggested to play a role in promoting the proliferation of cancer cells. In our previous study, we found that the expression of FNDC5 was higher in cancer than in normal tissues ( 18 , 19 ).…”

Section: Discussionmentioning

confidence: 99%

FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells

et al. 2022

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In this study, we aimed to reveal the resistance mechanism of hepatocellular carcinoma (HCC) cells to sorafenib by exploring the effect of FNDC5 on sorafenib-induced ferroptosis in HCC cells. We compared the expression level of FNDC5 between sorafenib-resistant and sorafenib-sensitive HCC cell lines and the level of ferroptosis between the groups after treatment with sorafenib. We knocked down FNDC5 in drug-resistant cell lines and overexpressed it in sorafenib-sensitive HCC cell lines to further demonstrate the role of FNDC5 in sorafenib-induced ferroptosis. Using PI3K inhibitors, we revealed the specific mechanism by which FNDC5 functions. In addition, we verified our findings obtained in in vitro experiments using a subcutaneous tumorigenic nude mouse model. The findings revealed that FNDC5 inhibits sorafenib-induced ferroptosis in HCC cells. In addition, FNDC5 activated the PI3K/Akt pathway, which in turn promoted the nuclear translocation of Nrf2 and increased the intracellular antioxidant response, thereby conferring resistance to ferroptosis. Our study provides novel insights for improving the efficacy of sorafenib.

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“…Various studies have also been conducted to investigate irisin’s role in other cancers [ 73 , 74 ]. It was found that an increase in the level of irisin leads to decreased proliferation, viability, and invasiveness in a lung cancer cell by inhibiting EMT mediated by the PI3K/Akt pathway [ 32 ].…”

Section: The Role Of Irisin In Human Pathophysiologymentioning

confidence: 99%

“…It was revealed that irisin could reverse IL-6-induced EMT by inhibiting the STAT3 pathway in osteosarcoma [ 74 ]. Irisin has been found to affect the expression of Snail (transcription factor), which is involved in EMT, and inhibits the transcription of the gene encoding E-cadherin, a characteristic of epithelial-derived cells [ 73 ]. A report showed that the level of irisin significantly increases in patients with renal tumors, hence suggesting that irisin can be used as a biomarker for renal cancer diagnosis [ 75 ].…”

Section: The Role Of Irisin In Human Pathophysiologymentioning

confidence: 99%

FNDC5/Irisin: Physiology and Pathophysiology

et al. 2022

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A sedentary lifestyle or lack of physical activity increases the risk of different diseases, including obesity, diabetes, heart diseases, certain types of cancers, and some neurological diseases. Physical exercise helps improve quality of life and reduces the risk of many diseases. Irisin, a hormone induced by exercise, is a fragmented product of FNDC5 (a cell membrane protein) and acts as a linkage between muscles and other tissues. Over the past decade, it has become clear that irisin is a molecular mimic of exercise and shows various beneficial effects, such as browning of adipocytes, modulation of metabolic processes, regulation of bone metabolism, and functioning of the nervous system. Irisin has a role in carcinogenesis; numerous studies have shown its impact on migration, invasion, and proliferation of cancer cells. The receptor of irisin is not completely known; however, in some tissues it probably acts via a specific class of integrin receptors. Here, we review research from the past decade that has identified irisin as a potential therapeutic agent in the prevention or treatment of various metabolic-related and other diseases. This article delineates structural and biochemical aspects of irisin and provides an insight into the role of irisin in different pathological conditions.

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The Role of Irisin in Cancer Disease

Cited by 27 publications

References 76 publications

Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx

Irisin Association with Ki-67, MCM3 and MT-I/II in Squamous Cell Carcinomas of the Larynx

FNDC5 Causes Resistance to Sorafenib by Activating the PI3K/Akt/Nrf2 Pathway in Hepatocellular Carcinoma Cells

FNDC5/Irisin: Physiology and Pathophysiology

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