1,721,064 research outputs found
Roles for microRNA 23b in regulating autophagy and development of pancreatic adenocarcinoma
No full textDescription of the roles for microRNA 23b in regulating autophagy and development of pancreatic adenocarcinoma
Mitochondrial metabolic alterations in cancer cells and related therapeutic targets
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Mutant p53 and mTOR/PKM2 regulation in cancer cells
No full textMutations of TP53 gene are the most common feature in aggressive malignant cells. In addition to the loss of the tumor suppressive role of wild-type p53, hotspot mutant p53 isoforms display oncogenic proprieties notoriously referred as gain of functions (GOFs) which result in chemoresistance to therapies, genomic instability, aberrant deregulation of cell cycle progression, invasiveness and enhanced metastatic potential, and finally, in patient poor survival rate. The identification of novel functional oncogenic pathways regulated by mutant p53 represent and intriguing topic for emerging therapies against a broad spectrum of cancer types bearing mutant TP53 gene. Mammalian target of rapamycin (mTOR), as well as pyruvate kinase isoform M2 (PKM2) are master regulators of cancer growth, metabolism, and cell proliferation. Herein, we report that GOF mutant R175H and R273H p53 proteins trigger PKM2 phosphorylation on Tyr 105 through the involvement of mTOR signaling. Our data, together with the newly discovered connection between mutant p53 and mTOR stimulation, raise important implications for the potential therapeutic use of synthetic drugs inhibiting mTOR/PKM2 axis in cancer cells bearing mutant TP53 gene. We further hypothesize that mTOR/PKM2 pathway stimulation serves to sustain the oncogenic activity of mutant p53 through both the enhancement of chemoresistance and of aerobic glycolysis of cancer cells. © 2016 IUBMB Life, 2016
Molecular interplay between mutant p53 proteins and autophagy in cancer cells
No full textAn increasing number of studies highlight the role of mutant p53 proteins in cancer cell growth and in the worsening of cancer patients' clinical outcome. Autophagy has been widely recognized as a main biological event involved in both the regulation of cancer cell proliferation and in the response of several anticancer drugs. A thorough analysis of scientific literature underlines the reciprocal interplay between mutant p53 proteins and autophagy regulation. In this review, we analytically summarize recent findings, which indicate that gain-of-function (GOF) mutant p53 proteins counteract the autophagic machinery by various molecular mechanisms including the regulation of AMPK and Akt/mTOR pathways, autophagy-related genes (ATGs), HIF-1α target genes, and the mitochondrial citrate carrier CIC. Moreover, we report that mutant p53 protein stability is affected by lysosome-mediated degradation through macroautophagy or chaperone-mediated autophagy, suggesting the use of autophagy stimulators to counteract mutant p53 oncogenic activity. Finally, we discuss the functional role of the interplay between mutant p53 proteins and autophagy in cancer progression, a fundamental knowledge to design more effective therapies against cancers bearing mutant TP53 gene
UCP2, a mitochondrial protein regulated at multiple levels
No full textAn ever-increasing number of studies highlightthe role of uncoupling protein 2 (UCP2) in a broadrange of physiological and pathological processes. Theknowledge of the molecular mechanisms of UCP2 regulationis becoming fundamental in both the comprehensionof UCP2-related physiological events and the identificationof novel therapeutic strategies based on UCP2 modulation.The study of UCP2 regulation is a fast-moving field.Recently, several research groups have made a great effortto thoroughly understand the various molecular mechanismsat the basis of UCP2 regulation. In this review, wedescribe novel findings concerning events that can occur ina concerted manner at various levels: Ucp2 gene mutation(single nucleotide polymorphisms), UCP2 mRNA and proteinexpression (transcriptional, translational, and proteinturn-over regulation), UCP2 proton conductance (ligandsand post-transcriptional modifications), and nutritional andpharmacological regulation of UCP2
Regulation of miR-23b expression and its dual role on ROS production and tumour development
No full textAmong the wide family of microRNAs, microRNA 23b (miR-23b) intriguingly assumes opposite roles on regulation of reactive oxygen species (ROS) and on the development of human cancers. In this review we describe novel findings concerning the molecular events involved in miR-23b gene activation or repression and in both ROS regulation and tumour development. In particular, we define the molecular targets of miR-23b that determine its function as either a tumour suppressor or oncomir in different cell types. Finally, we analyze the involvement of miR-23b in cancer cell metabolism, including autophagy, and in biomarker signatures of microRNAs allowing a prognostic and therapeutic evaluation in various human cancers
Proteomics in pancreatic cancer research.
No full textIn this review, we give an overview of the actual role of proteomic technologies in the study of
pancreatic cancers (PCs). We describe PC proteomics on the basis of sample origins, i.e.
tissues, body fluids, and PC cell lines. As regards PC tissues, we report the identification of a
number of candidate biomarkers of precursor lesions that may allow early diagnosis of this
neoplasia. Moreover, we describe cytoskeletal and hypoxia-regulated proteins that confirm the
involvement of cytoskeleton modifications and metabolism adaptations in carcinogenesis. We
also discuss the most important biomarkers identified by proteomic analysis involved in local
invasion and distant metastasis, and in the cross-talk between pancreatic tumor and the
surrounding stroma. Furthermore, we report novel candidate biomarkers identified in serum,
plasma, and pancreatic juice of cancer patients compared with cancer-free controls. Proteomic
alterations in PC cell line models as compared to normal controls and studies on cell
lines treated with drugs or new agents to understand their mechanism of pharmacological
action or the onset of drug resistance are also presented. Finally, we discuss the recent
improvements obtained in classical 2-DE and high-throughput proteomic strategies able to
allow the overcoming of relevant proteomic drawbacks
Autocrine mechanisms of cancer chemoresistance
No full textAn ever-increasing number of studies highlight the role of cancer secretome in the modification of tumour microenvironment and in the acquisition of cancer cell resistance to therapeutic drugs. The knowledge of the mechanisms underlying the relationship between cancer cell-secreted factors and chemoresistance is becoming fundamental for the identification of novel anticancer therapeutic strategies overcoming drug resistance and novel prognostic secreted biomarkers. In this review, we summarize the novel findings concerning the regulation of secreted molecules by cancer cells compromising drug sensitivity. In particular, we highlight data from available literature describing the involvement of cancer cell-secreted molecules determining chemoresistance in an autocrine manner, including: i) growth factors; ii) glycoproteins; iii) inflammatory cytokines; iv) enzymes and chaperones; and v) tumor-derived exosomes
Metastatic outgrowth via the two-way interplay of autophagy and metabolism
No full textMetastasis represents one of the most dangerous issue of cancer progression, characterized by intricate interactions between invading tumor cells, various proteins, and other cells on the way towards target sites. Tumor cells, while undergoing metastasis, engage in dynamic dialogues with stromal cells and undertake epithelial-mesenchymal transition (EMT) phenoconversion. To ensure survival, tumor cells employ several strategies such as restructuring their metabolic needs to adapt to the alterations of the microenvironmental resources via different mechanisms including macroautophagy (autophagy) and to circumvent anoikis-a form of cell death induced upon detachment from the extracellular matrix (ECM). This review focuses on the puzzling connections of autophagy and energetic metabolism within the context of cancer metastasis
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