Reviews

Hepatic stress associated with pathologies characterized by disturbed glucose production

Monika Gjorgjieva1-3,#, Gilles Mithieux1-3 and Fabienne Rajas1-3

LIVER FUNCTION IN GLUCOSE PRODUCTION AND NORMOGLYCEMIA Maintaining normal glucose levels in the organism i.e. between 0.7 to 1.1 g/L, is a complex task, involving a multi-organ crosstalk responsible for

Metabolic and functional reprogramming of myeloid-derived suppressor cells and their therapeutic control in glioblastoma

Woong-Jai Won1, Jessy S. Deshane2, Jianmei W. Leavenworth3, Claudia R. Oliva4 and Corinne E. Griguer4

Glioblastoma, also known as glioblastoma multiforme, is the most common and deadliest form of high-grade malignant brain tumors with limited available treatments. Within the glioblastoma tumor microenvironment (TME), tumor cells, stromal cells, and infiltrating immune cells continuously interact and exchange signals through various secreted factors including cytokines, chemokines, growth factors, and metabolites. Simultaneously, they dynamically reprogram their metabolism according to environmental energy demands such as hypoxia and neo-vascularization. Such metabolic reprogramming can determine fates and functions of tumor cells as well as immune cells. Ultimately, glioma cells in the TME transform immune cells to suppress anti-tumor immune cells such as T, natural killer (NK) cells, and dendritic cells (DC), and evade immune surveillance, and even to promote (...)

R-loops: formation, function, and relevance to cell stress

David F Allison1,2 and Gang Greg Wang1,2

INTRODUCTION A variety of topological, structural and hybridization events occur during DNA replication and gene transcription. Unwinding of the DNA double helix provides access for polymerase to a template strand,

Control of nucleolar stress and translational reprogramming by lncRNAs

Yvessa Verheyden1, Lucas Goedert1,2 and Eleonora Leucci1

INTRODUCTION Unfavourable environmental conditions trigger cellular responses that help minimize and/or repair the damage experienced by the cell. During stress responses, most of the biosynthetic processes of the cell are

Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress

Florian Lang1, Christos Stournaras2, Nefeli Zacharopoulou2, Jakob Voelkl3,4, Ioana Alesutan3,4,5

INTRODUCTION The ubiquitously expressed [1][2][3][4] serum- and glucocorticoid-inducible kinase 1 (SGK1) has originally been cloned as a gene up-regulated by serum and glucocorticoids in rat mammary tumor cells [1][5]. The

Regulation of T cell antitumor immune response by tumor induced metabolic stress

Fanny Chalmin1,2,3,4, Mélanie Bruchard1,2,3,4, Frederique Vegran1,2,3,4 and Francois Ghiringhelli1,2,3,4

Adaptive T cell immune response is essential for tumor growth control. The efficacy of immune checkpoint inhibitors is regulated by intratumoral immune response. The tumor microenvironment has a major role in adaptive immune response tuning. Tumor cells generate a particular metabolic environment in comparison to other tissues. Tumors are characterized by glycolysis, hypoxia, acidosis, amino acid depletion and fatty acid metabolism modification. Such metabolic changes promote tumor growth, impair immune response and lead to resistance to therapies. This review will detail how these modifications strongly affect CD8 and CD4 T cell functions and impact immunotherapy efficacy.

The role of metabolic adaptation to nutrient stress in pancreatic cancer

Abhishek Derle1,#, Maria Chiara De Santis1,#, Luca Gozzelino1,#, Edoardo Ratto1,# and Miriam Martini1

INTRODUCTION Pancreatic cancer is the fourth leading cause of cancer death in the developed world [1]. The most common subtype of pancreatic cancer is pancreatic ductal adenocarcinomas (PDACs) that arise

Systemic signalling and local effectors in developmental stability, body symmetry, and size

Sergio Juarez-Carreño1, Javier Morante1 and Maria Dominguez1

Symmetric growth and the origins of fluctuating asymmetry are unresolved phenomena of biology. Small, and sometimes noticeable, deviations from perfect bilateral symmetry reflect the vulnerability of development to perturbations. The degree of asymmetry is related to the magnitude of the perturbations and the ability of an individual to cope with them. As the left and right sides of an individual were presumed to be genetically identical, deviations of symmetry were traditionally attributed to non-genetic effects such as environmental and developmental noise. In this review, we draw attention to other possible sources of variability, especially to somatic mutations and transposons. Mutations are a major source of phenotypic variability and recent genomic data have highlighted somatic mutations as ubiquitous, even in phenotypically normal individuals. We discuss the importance of factors that are responsible for buffering and stabilizing the genome (...)

Making the final cut: pathogenic amyloid-β peptide generation by γ-secretase

Harald Steiner1,2, Akio Fukumori3, Shinji Tagami4 and Masayasu Okochi4

Alzheimer´s disease (AD) is a devastating neurodegenerative disease of the elderly population. Genetic evidence strongly suggests that aberrant generation and/or clearance of the neurotoxic amyloid-β peptide (Aβ) is triggering the disease. Aβ is generated from the amyloid precursor protein (APP) by the sequential cleavages of β- and γ-secretase. The latter cleavage by γ-secretase, a unique and fascinating four-component protease complex, occurs in the APP transmembrane domain thereby releasing Aβ species of 37-43 amino acids in length including the longer, highly pathogenic peptides Aβ42 and Aβ43. The lack of a precise understanding of Aβ generation as well as of the functions of other γ-secretase substrates has been one factor underlying the disappointing failure of γ-secretase inhibitors in clinical trials, but on the other side also been a major driving force for structural and in depth mechanistic studies on this key AD drug target in the past few years. Here we (...)

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