p63 Isoforms Regulate Metabolism of Cancer Stem Cells

D’Aguanno, Simona; Barcaroli, Daniela; Rossi, Cláudia; Zucchelli, Mirco; Ciavardelli, Domenico; Cortese, Claudio; Cola, Antonella De; Volpe, Stefano; D’Agostino, Daniela; Todaro, Matilde; Stassi, Giorgio; Ilio, Carmine Di; Urbani, Andrea; Laurenzi, Vincenzo De

doi:10.1021/pr4012574

Cited by 28 publications

(21 citation statements)

References 70 publications

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“…Blots were probed with the following polyclonal antisera: HMGB1, HMGB2, Sin 3A, HTT, PSMA5, PDIA3, and NF-B (from Abcam). One hundred micrograms of liver protein lysates was separated in the first dimension on IPG gels (pH 3-10, nonlinear; GE Healthcare) (8). The two-dimensional separation was performed on 4 -20% SDS polyacrylamide gels.…”

Section: Methodsmentioning

confidence: 99%

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology

Capuani

Della-Morte

Donadel

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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It is under a complex control by substrates such as hormones, nutrients, and neuronal impulses. Insulin promotes glycogen synthesis, lipogenesis, and lipoprotein synthesis and inhibits gluconeogenesis, glycogenolysis, and VLDL secretion by modifying the expression and enzymatic activity of specific molecules. To understand the pathophysiological mechanisms leading to metabolic liver disease, we analyzed liver protein patterns expressed in a mouse model of diabetes by proteomic approaches. We used insulin receptor-knockout (IR Ϫ/Ϫ ) and heterozygous (IR ϩ/Ϫ ) mice as a murine model of liver metabolic dysfunction associated with diabetic ketoacidosis and insulin resistance. We evaluated liver fatty acid levels by microscopic examination and protein expression profiles by orthogonal experimental strategies using protein 2-DE MALDI-TOF/TOF and peptic nLC-MS/MS shotgun profiling. Identified proteins were then loaded into Ingenuity Pathways Analysis to find possible molecular networks. Twenty-eight proteins identified by 2-DE analysis and 24 identified by nLC-MS/MS shotgun were differentially expressed among the three genotypes. Bioinformatic analysis revealed a central role of high-mobility group box 1/2 and huntigtin never reported before in association with metabolic and related liver disease. A different modulation of these proteins in both blood and hepatic tissue further suggests their role in these processes. These results provide new insight into pathophysiology of insulin resistance and hepatic steatosis and could be useful in identifying novel biomarkers to predict risk for diabetes and its complications. insulin resistance; huntigtin; high-mobility group-B1; proteomics TYPE 2 DIABETES (T2D) is a complex metabolic disorder characterized by increased levels of insulin resistance and impaired ␤-cell function with reduced insulin secretion (35). In T2D, modification of hepatic metabolism is associated with glucose and lipid overproduction, leading to overt hyperglycemia and diabetic dyslipidemia. Glucose overproduction is a physiological response in T2D, whereas the overproduction of lipids linked with insulin resistance remains a phenomenon to clarify since insulin increases abundance of lipogenic enzymes and insulin resistance diminishes lipogenesis (31, 41). Furthermore, insulin resistance and T2D are linked with hepatic steatosis, which is an exacerbation of liver dysfunction generated by accumulation of lipids, mainly triglycerides (23).Several etiological mechanisms have been proposed to explain the pathological link between insulin resistance, T2D, and liver disease, including inflammation and oxidative stress (36). Recently, novel anti-inflammatory proteins called chaperones and Toll-like receptors (TLRs) have been suggested to play a significant role in this pathological process (27). However, to date, the molecular mechanisms linking the impairment in glucose homeostasis with liver disease are not fully understood.Therefore, elucidation of molecular alterations, which regulate metabolic liver dysfunct...

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Section: Methodsmentioning

confidence: 99%

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology

Capuani

Della-Morte

Donadel

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…Scores of 10 or higher (negative log of the P-value) have a high confidence of not being generated by random chance alone. 23,33,34 Western blot analysis. Cells were lysed by sonication in 10 mM Tris-HCl, pH 7.4, 2% SDS, in the presence of proteases inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Affinity purification-mass spectrometry analysis of bcl-2 interactome identified SLIRP as a novel interacting protein

D’Aguanno¹,

Trisciuoglio²,

Desideri³

et al. 2016

European Journal of Cancer

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“…Generally in the clinical settings, molecular markers may be used to test groups of patients with certain disorders and compare their metabolic profile with a normal control group, since some diseases may result from a chronic alteration of normal metabolism [42][43][44][45][46][47][48].…”

Section: Metabolomic Mus Biomarkersmentioning

confidence: 99%

Integration of metabolomics and proteomics in multiple sclerosis: From biomarkers discovery to personalized medicine

Boccio

Rossi

Ioia

et al. 2016

Proteomics Clinical Apps

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Personalized medicine is the science of individualized prevention and therapy. In the last decade, advances in high-throughput approaches allowed the development of proteomic and metabolomic studies in evaluating the association of genetic and phenotypic variability with disease sensitivity and analgesic response. These considerations have more value in case of multiple sclerosis (MuS), a multifactorial disease with high heterogeneity in clinical course and treatment response. In this review, we reported and updated about proteomic and metabolomic studies for the research of new candidate biomarkers in MuS, and difficulties in their clinical applications. We focused especially on the description of both "omics" approaches that, once integrated, may synergically describe pathophysiology conditions. To prove this assumption, we rebuilt interaction between proteins and metabolites described in the literature as potential biomarkers for MuS, and a pathway analysis of these molecules was performed. The result of such speculation demonstrated a strong convergence of proteomic and metabolomic results in this field, showing also a poorness of available tools for incorporating "omics" approaches. In conclusion, the integration of Metabolomics and Proteomics may allow a more complete characterization of such a heterogeneous disease, providing further insights into personalized healthcare.

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p63 Isoforms Regulate Metabolism of Cancer Stem Cells

Cited by 28 publications

References 70 publications

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology

Affinity purification-mass spectrometry analysis of bcl-2 interactome identified SLIRP as a novel interacting protein

Integration of metabolomics and proteomics in multiple sclerosis: From biomarkers discovery to personalized medicine

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