ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma

Frezza, Valentina; Fernanda, Cláudia; Gatti, Elena; Peschiaroli, Angelo; Lena, Anna Maria; Petruzzelli, M A; Candi, Eleonora; Anemona, Lucia; Mauriello, Alessandro; Pelicci, Pier Giuseppe; Melino, Gerry; Bernassola, Francesca

doi:10.18632/aging.101725

Cited by 14 publications

(14 citation statements)

References 94 publications

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“…Accordingly, we showed that during keratinocyte differentiation there was a depression of the glucose metabolism (Figure 3C,D). Moreover, ΔNp63 is able to control the insulin receptor substrate (IRS) IRS1 [36], and in our p63RNAi experiments, it also controls IRS4 (Table S1, last row), both of which are responsible of the re-localization of GLUT4 transporter [37] on the plasma membrane, explaining the mechanism of glucose uptake impairment observed during differentiation.…”

Section: Discussionmentioning

confidence: 99%

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes

Palombo

Caporali

Falconi

et al. 2019

IJMS

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Flavonoids have been demonstrated to affect the activity of many mammalian enzyme systems. Their functional phenolic groups are able to mediate antioxidant effects by scavenging free radicals. Molecules of this class have been found able to modulate the activity of kinases, phospholipase A2, cyclooxygenases, lipoxygenase, glutathione S-transferase, and many others. Recently, it has been demonstrated that luteolin, in the form of Luteolin-7-O-β-d-glucoside (LUT-7G) is able to induce the keratinocyte differentiation process in vitro. This flavonoid is able to counteract the proliferative effects of IL-22/IL6 pathway by the inhibition of STAT3 activity also in vivo in a psoriatic mouse model. Observations on energy metabolism changes of differentiating cells led us to perform a complete metabolomics analysis using human primary keratinocytes treated with LUT-7G. Our results show that LUT-7G, is not only able to impair the nuclear translocation of STAT3, but it also blocks the energy metabolism pathway, depressing the glycolytic and Krebs pathway by the inhibition of hexokinase 2 activity. These data confirm that LUT-7G can be proposed as a potential candidate for the treatment of inflammatory and proliferative diseases, but its role as a hexokinase 2 (HEK2) inhibitor opens new perspectives in nutritional science, and especially in cancer therapy, in which the inhibition of the Warburg effect could be relevant.

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Section: Discussionmentioning

confidence: 99%

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes

Palombo

Caporali

Falconi

et al. 2019

IJMS

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“…The IRS family includes four isoforms, IRS1-4 (Al-Salam and Irwin 2017;Machado-Neto et al 2018). IRS1 is a mediator of insulin and IGF1, both of which can bind to INSR (Simpson et al 2017;Frezza et al 2018). The PI3K/protein kinase B (also known as Akt) signalling pathway is mediated by IRS2 and plays an important role in cell growth, proliferation, and apoptosis (Lei et al 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Phosphorylated INSR and IGF1R activate common substrates for downstream effector networks, including IRS, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase pathways (Frezza et al. 2018 ). Insulin and IGF1 bind and phosphorylate INSR and IGF1R, respectively.…”

Section: Discussionmentioning

confidence: 99%

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells

Wang

Shan

Duan

et al. 2020

Pharmaceutical Biology

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Context: The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown. Objective: This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway. Materials and methods: Sixteen-month-old male Wistar rats in the Heshouwuyin group and the naturalaging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group (n ¼ 10). The testicular tissue and spermatogenic cells were studied. Results: The immunofluorescence results revealed that the insulin receptor (INSR)-(0.056 ± 0.00548), insulin receptor substrate 1(IRS1)-(0.251 ± 0.031), IRS2 (0.230 ± 0.019)-and insulin-like growth factor 1 (IGF1)positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031; p < 0.01), and the IGF-binding protein 3 (IGFBP3)positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group (p < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells. Conclusions: Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.

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“…Гормони молока можуть мати негативний вплив на здоров'я споживачів. Зокрема занепокоєння викликає ряд публікацій (Rogers et al, 2006;Duarte-Salles et al, 2014;Frezza et al, 2018;Rieunier et al, 2019), котрі пов'язують виникнення онкологічних захворювань зі споживанням молока та молочних продуктів. Пояснюється це наявністю у молоці низки гормонів, зокрема інсуліноподібного фактору росту, пролактину, простагландинів, глюкокортикоїдів, естрогенів та інших гормонів (Malekinejad & Rezabakhsh, 2015).…”

Section: вступunclassified

The concentration of triiodothyronine and thyroxine in colostrum, milk and plasma of cows

Pan’kiv¹,

Simonov²

2020

SMLNUVMB

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Milk contains key nutrients in optimal proportions, which makes it to be an important component of the human diet. Despite the fact that consumers receive with milk a significant amount of readily available nutrients, milk can be a source of dangerous factors of chemical and biological origin. The level of physiological hormones found in milk is not a limiting factor and is studied solely for scientific purposes. However, milk hormones can have a negative effect on the health of consumers. Based on this, the aim of this work was to study the concentration of triiodothyronine and thyroxine in colostrum, milk and blood plasma of cows at different stages of lactation. The secretion of the mammary gland and blood plasma of cows of Ukrainian black-and-white dairy breed, in their 2nd–5th lactations with milk yield 5100–5700 kg of milk per previous lactation was the object of the study. The concentration of triiodothyronine and thyroxine using enzyme-linked immunosorbent assay was investigated in withdrawn samples. The obtained data indicates that the highest level of secretion of iodine-containing thyroid hormones with milk is observed on 1st–4th days of lactation. Thereafter, the concentration of hormones in milk statistically significant decreases by 2.8–3-fold (P ˂ 0.001) till 30–40th day of lactation. The high concentration of iodine-containing hormones in colostrum allows to enhance metabolic processes in calves. Studies of the concentration of thyroid hormones in the blood plasma of cows showed a gradual increase from the beginning of lactation till 10th–14th and then till 30th–40th days of lactation. By 10th–14th days we observed 2.2-fold growth of triiodothyronine level (P ˂ 0.001), and till 30th–40th days this parameter has increased by another 12.5 %. The level of thyroxine on 10th–14th days of lactation was higher, compared to such in the beginning of lactation by 62.2 % (P ˂ 0.001), and by 30th–40th day increase was by 40.9 %. The main reasons for such changes are the formation of lactation dominant, the discharge of hormones secreted by the breast and the stimulation of metabolic processes during lactation. The prospects of further research lie in investigation of the dependence of triiodothyronine and thyroxine levels in the secretion of the mammary gland on productivity, breed, age and diet of animals.

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ΔNp63 promotes IGF1 signalling through IRS1 in squamous cell carcinoma

Cited by 14 publications

References 94 publications

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes

Luteolin-7-O-β-d-Glucoside Inhibits Cellular Energy Production Interacting with HEK2 in Keratinocytes

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells

The concentration of triiodothyronine and thyroxine in colostrum, milk and plasma of cows

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