Volume 3 (2019)
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
Stress granules regulate paraspeckles: RNP granule continuum at work
Haiyan An1 and Tatyana A. Shelkovnikova1
Eukaryotic cells contain a variety of large, multicomponent RNA-protein complexes termed ribonucleoprotein (RNP) granules. RNP granules represent membraneless organelles – biomolecular condensates lacking a membrane and maintained through an intricate
LTX-315 – a promising novel antitumor peptide and immunotherapeutic agent
Dagmar Zweytick1,2
Host defense in mammals, as provided by the innate immune system, comprises proteins such as lactoferrin (LF), a multifunctional iron-binding glycoprotein originally discovered in bovine milk. LF is further pepsin-cleaved
Endoplasmic reticulum and Golgi stress in microcephaly
Sandrine Passemard1,2, Franck Perez3, Pierre Gressens1,4 and Vincent El Ghouzzi1
Microcephaly is a neurodevelopmental condition characterized by a small brain size associated with intellectual deficiency in most cases and is one of the most frequent clinical sign encountered in neurodevelopmental disorders. It can result from a wide range of environmental insults occurring during pregnancy or postnatally, as well as from various genetic causes and represents a highly heterogeneous condition. However, several lines of evidence highlight a compromised mode of division of the cortical precursor cells during neurogenesis, affecting neural commitment or survival as one of the common mechanisms leading to a limited production of neurons and associated with the most severe forms of congenital microcephaly. In this context, the emergence of the endoplasmic reticulum (ER) and the Golgi apparatus as key guardians of cellular homeostasis, especially through the regulation of proteostasis, has raised the hypothesis that pathological ER and/or Golgi stress could contribute significantly to cortical impairments eliciting microcephaly. In (…)
LTX-315 sequentially promotes lymphocyte-independent and lymphocyte-dependent antitumor effects
Hsin-Wei Liao1,#, Christopher Garris1,#, Christina Pfirschke1, Steffen Rickelt2, Sean Arlauckas1, Marie Siwicki1, Rainer H. Kohler1, Ralph Weissleder1, Vibeke Sundvold-Gjerstad3, Baldur Sveinbjørnsson3,4, Øystein Rekdal3,4 and Mikael J. Pittet1
LTX-315 is an oncolytic peptide that has antitumor efficacy in mice grafted with various tumor cell lines and is currently being tested in phase II clinical trials. Here we aimed to further evaluate LTX-315 in conditional genetic mouse models of cancer that typically resist current treatment options and to better understand the drug’s mode of action in vivo. We report LTX-315 mediates profound antitumor effects against Braf- and Pten-driven melanoma and delays the progression of Kras- and P53-driven soft tissue sarcoma in mice. Additionally, we show in melanoma that LTX-315 triggers two sequential phases of antitumor response. The first phase of response, which begins within minutes of drug delivery into tumors, is defined by disrupted tumor vasculature and decreased tumor burden and occurs independently of (...)
Anti-regulatory T cells are natural regulatory effector T cells
Niels Ødum 1
It is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have
Stress granules regulate paraspeckles: RNP granule continuum at work
Haiyan An1 and Tatyana A. Shelkovnikova1
Eukaryotic cells contain a variety of large, multicomponent RNA-protein complexes termed ribonucleoprotein (RNP) granules. RNP granules represent membraneless organelles – biomolecular condensates lacking a membrane and maintained through an intricate
Endoplasmic reticulum and Golgi stress in microcephaly
Sandrine Passemard1,2, Franck Perez3, Pierre Gressens1,4 and Vincent El Ghouzzi1
Microcephaly is a neurodevelopmental condition characterized by a small brain size associated with intellectual deficiency in most cases and is one of the most frequent clinical sign encountered in neurodevelopmental disorders. It can result from a wide range of environmental insults occurring during pregnancy or postnatally, as well as from various genetic causes and represents a highly heterogeneous condition. However, several lines of evidence highlight a compromised mode of division of the cortical precursor cells during neurogenesis, affecting neural commitment or survival as one of the common mechanisms leading to a limited production of neurons and associated with the most severe forms of congenital microcephaly. In this context, the emergence of the endoplasmic reticulum (ER) and the Golgi apparatus as key guardians of cellular homeostasis, especially through the regulation of proteostasis, has raised the hypothesis that pathological ER and/or Golgi stress could contribute significantly to cortical impairments eliciting microcephaly. In (…)
The impact of endothelial cell death in the brain and its role after stroke: A systematic review
Marietta Zille1, Maulana Ikhsan1, Yun Jiang1,2, Josephine Lampe1,2, Jan Wenzel1,2 and
Markus Schwaninger1,2
INTRODUCTION The brain is a metabolically active organ that consumes about 20% of the total energy of the body [1]. At the same time, it is unable to store significant
Unraveling the molecular principles by which ceramides commit cells to death
Shashank Dadsena1, Dina G. Hassan1 and Joost C.M. Holthuis1
EMERGENCE OF CERAMIDES AS TUMOR SUPPRESSOR LIPIDS Sphingolipids are unusually versatile membrane components that participate in mechanical stability, signaling, and molecular sorting. As the path to their production is paved
Immunosurveillance of cancer cell stress
Seila Lorenzo-Herrero1-3, Christian Sordo-Bahamonde1-3, Segundo González1-3 and Alejandro López-Soto1-3
Cancer development is tightly controlled by effector immune responses that recognize and eliminate malignantly transformed cells. Nonetheless, certain immune subsets, such as tumor-associated macrophages, have been described to promote tumor growth, unraveling a double-edge role of the immune system in cancer. Cell stress can modulate the crosstalk between immune cells and tumor cells, reshaping tumor immunogenicity and/or immune function and phenotype. Infiltrating immune cells are exposed to the challenging conditions typically present in the tumor microenvironment. In return, the myriad of signaling pathways activated in response to stress conditions may tip the balance toward stimulation of antitumor responses or immune-mediated tumor progression. Here, we explore how distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression.
Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity
Maite Alvarez1,2, Itziar Otano1,2, Luna Minute1,2, Maria Carmen Ochoa1,2,3, Elisabeth Perez-Ruiz1,4, Ignacio Melero1,2,3,5,6 and Pedro Berraondo1,2,3
Inhibitory checkpoint blockade (ICB) immunotherapy has produced very significant advances in the fight against cancer (Figure 1). The synergistic combination of PD-1 and CTLA-4 blockade therapy has been successfully used
LTX-315 – a promising novel antitumor peptide and immunotherapeutic agent
Dagmar Zweytick1,2
Host defense in mammals, as provided by the innate immune system, comprises proteins such as lactoferrin (LF), a multifunctional iron-binding glycoprotein originally discovered in bovine milk. LF is further pepsin-cleaved
Anti-regulatory T cells are natural regulatory effector T cells
Niels Ødum 1
It is well established that the immune system uses regulatory immune-suppressive cells to inhibit and terminate immune reactions and maintain immune balance. In the last decade, Andersen and colleagues have
The targeting of tumor-associated macrophages by vaccination
Mads Hald Andersen1,2,3
Immune suppressive myeloid cells include a heterogenous population of cells that include tumor-associated macrophages (TAMs). TAMs are major players in inducing the immunosuppressive microenvironment associated with many tumors. These lesions
Mitochondrial stress delays tumorigenesis in a Li-Fraumeni syndrome mouse model
Matthew P. Donnelly1, Jie Li1 and Paul M. Hwang1
As a prominent hub of metabolic activity, the mitochondrion can initiate retrograde signaling in response to bioenergetic stress that is important for various adaptive changes including cell cycle regulation [1][2].
Mitochondria organize the cellular proteostatic response and promote cellular senescence
Yanjun Li1, Lei Liu2, Yushan Zhu1 and Quan Chen1,2
Timely disposal and degradation of misfolded proteins and their aggregates is critical for cellular proteostasis and the well-being of a cell. During evolution, cells have acquired a sophisticated system to
Could de-stressing the brain be the solution for long-term weight loss?
Florian Seyfried1 and Mohammed K. Hankir2
INTRODUCTION One just needs to take a look at a typical vending machine (often found in hospitals) to appreciate what has happened to our food and drink. The relatively sudden