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Trends in Cell Biology

Barbara J Mann, Patricia Wadsworth
Chromosome segregation during cell division requires a bipolar mitotic spindle. Therefore, how the spindle is formed, maintained, and functions is of fundamental importance for all eukaryotic cells. Members of the evolutionarily conserved kinesin-5 family of motor proteins have been shown to play an essential role in spindle formation by generating forces that establish and maintain spindle bipolarity and contribute to spindle elongation. Recent work demonstrates that accessory proteins and post-translational modifications regulate the localization and activity of kinesin-5 motors in cells...
September 13, 2018: Trends in Cell Biology
Lorenzo Galluzzi, Stefani Spranger, Elaine Fuchs, Alejandro López-Soto
Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy...
September 13, 2018: Trends in Cell Biology
Joppe Nieuwenhuis, Thijn R Brummelkamp
Microtubules are subjected to a variety of post-translational modifications (PTMs). The combination of different α- and β-tubulin isoforms and PTMs are referred to as the tubulin code. PTMs are generated by a suite of enzymes thought to affect tubulin-interacting proteins. One PTM is the cyclic removal and ligation of the C-terminal tyrosine of α-tubulin. This has been implicated in cellular processes such as mitosis, cardiomyocyte contraction, and neuronal function. Recently, vasohibins (VASHs) were identified as the first tubulin-detyrosinating enzymes, A cell-autonomous role for VASHs in regulating the cytoskeleton was unexpected due to their previous association with angiogenesis...
September 10, 2018: Trends in Cell Biology
António J M Santos, Yuan-Hung Lo, Amanda T Mah, Calvin J Kuo
The intestinal epithelium is a rapidly renewing cellular compartment. This constant regeneration is a hallmark of intestinal homeostasis and requires a tightly regulated balance between intestinal stem cell (ISC) proliferation and differentiation. Since intestinal epithelial cells directly contact pathogenic environmental factors that continuously challenge their integrity, ISCs must also actively divide to facilitate regeneration and repair. Understanding niche adaptations that maintain ISC activity during homeostatic renewal and injury-induced intestinal regeneration is therefore a major and ongoing focus for stem cell biology...
September 5, 2018: Trends in Cell Biology
Urjita Joshi, Joseline A Houwman, Peter van der Sluijs
Lysosome function and position in the cytoplasm depends on the BORCS machinery, which tethers lysosomes to the kinesin microtubule motor. A recent paper of Snouwaert et al. in Cell Reports characterizes a mouse with a spontaneous mutation in the Borcs7 subunit, which causes axonal dystrophy and impaired motor function.
September 2, 2018: Trends in Cell Biology
Helen Loo Yau, Ilias Ettayebi, Daniel D De Carvalho
During cancer initiation and progression, the somatic epigenome is broadly reprogrammed. This reprogramming can be a consequence of several processes, including altered transcriptional profiles and mutations. In addition, immune cells infiltrating the tumor microenvironment display a reprogrammed epigenome. For instance, tumor infiltrating T cells frequently exhibit an exhausted phenotype characterized by aberrant DNA methylation. Moreover, these aberrant epigenomes of cancer cells and infiltrating immune cells may represent a cancer vulnerability...
August 25, 2018: Trends in Cell Biology
Abigail K Corona, William T Jackson
Autophagosome/amphisome-lysosome fusion is a highly regulated process at the protein, lipid, and biochemical level. Each primary component of fusion, such as the core SNAREs, HOPS complex, or physical positioning by microtubule-associated dynein motors, are regulated at multiple points to ensure optimum conditions for autophagic flux to proceed. With the complexity of the membrane fusion system, it is not difficult to imagine how autophagic flux defect-related disorders, such as Huntington's disease, non-familial Alzheimer's disease, and Vici syndrome develop...
August 13, 2018: Trends in Cell Biology
Elodie Villa, Sandrine Marchetti, Jean-Ehrland Ricci
Mitochondria are essential highly dynamic organelles that provide the necessary energy for a variety of different processes, such as survival, proliferation, and migration. In order to maintain an intact mitochondrial network, cells have developed quality control systems that allow the removal of damaged or superfluous mitochondria by selective mitochondrial autophagy called mitophagy. Although the parkin/PINK1 axis is often considered the main regulator of mitophagy, a growing body of evidence has shown that this pathway is not unique and that mitophagy can still be functional in the absence of parkin...
August 13, 2018: Trends in Cell Biology
David Ribet, Pascale Cossart
Manipulation of host protein post-translational modifications (PTMs) is used by various pathogens to interfere with host cell functions. Among these modifications, ubiquitin (UBI) and ubiquitin-like proteins (UBLs) constitute key targets because they are regulators of pathways essential for the host cell. In particular, these PTM modifiers control pathways that have been described as crucial for infection such as pathogen entry, replication, propagation, or detection by the host. Although bacterial pathogens lack eucaryotic-like UBI or UBL systems, many of them produce proteins that specifically interfere with these host PTMs during infection...
August 11, 2018: Trends in Cell Biology
Mary Williard Elting, Pooja Suresh, Sophie Dumont
The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle...
August 6, 2018: Trends in Cell Biology
Kerrie E McNally, Peter J Cullen
Endosomes are major protein sorting stations in cells. Endosomally localised multi-protein complexes sort integral proteins, including signaling receptors, nutrient transporters, adhesion molecules, and lysosomal hydrolase receptors, for lysosomal degradation or conversely for retrieval and subsequent recycling to various membrane compartments. Correct endosomal sorting of these proteins is essential for maintaining cellular homeostasis, with defects in endosomal sorting implicated in various human pathologies including neurodegenerative disorders...
July 30, 2018: Trends in Cell Biology
Shom Goel, Molly J DeCristo, Sandra S McAllister, Jean J Zhao
Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have recently entered the therapeutic armamentarium of clinical oncologists, and show promising activity in patients with breast and other cancers. Although their chief mechanism of action is inhibition of retinoblastoma (RB) protein phosphorylation and thus the induction of cell cycle arrest, CDK4/6 inhibitors alter cancer cell biology in other ways that can also be leveraged for therapeutic benefit. These include modulation of mitogenic kinase signaling, induction of a senescence-like phenotype, and enhancement of cancer cell immunogenicity...
July 27, 2018: Trends in Cell Biology
Karol Fiedorczuk, Leonid A Sazanov
Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I...
July 25, 2018: Trends in Cell Biology
Ana Rita Nobre, David Entenberg, Yarong Wang, John Condeelis, Julio A Aguirre-Ghiso
Hypoxia is linked to metastasis; however, how it affects metastatic progression is not clear due to limited consensus in the literature. We posit that this lack of consensus is due to hypoxia being studied using different approaches, such as in vitro, primary tumor, or metastasis assays in an isolated manner. Here, we review the pros and cons of in vitro hypoxia assays, highlight in vivo studies that inform on physiological hypoxia, and review the evidence that primary tumor hypoxia might influence the fate of disseminated tumor cells (DTCs) in secondary organs...
July 21, 2018: Trends in Cell Biology
Lars Langemeyer, Florian Fröhlich, Christian Ungermann
Eukaryotic cells maintain a highly organized endolysosomal system. This system regulates the protein and lipid content of the plasma membrane, it participates in the intracellular quality control machinery and is needed for the efficient removal of damaged organelles. This complex network comprises an endosomal membrane system that feeds into the lysosomes, yet also allows recycling of membrane proteins, and probably lipids. Moreover, lysosomal degradation provides the cell with macromolecules for further growth...
July 16, 2018: Trends in Cell Biology
Patrick T Caswell, Tobias Zech
Cell migration controls developmental processes (gastrulation and tissue patterning), tissue homeostasis (wound repair and inflammatory responses), and the pathobiology of diseases (cancer metastasis and inflammation). Understanding how cells move in physiologically relevant environments is of major importance, and the molecular machinery behind cell movement has been well studied on 2D substrates, beginning over half a century ago. Studies over the past decade have begun to reveal the mechanisms that control cell motility within 3D microenvironments - some similar to, and some highly divergent from those found in 2D...
June 30, 2018: Trends in Cell Biology
Edward E Morrisey, Anil K Rustgi
Lung and esophageal development and organogenesis involve a complex interplay of signaling pathways and transcriptional factors. Once the lung and esophagus do separate, their epithelial proliferation and differentiation programs share certain common properties that may fuel adaptive responses to injury and subsequent regeneration. Lung and esophageal tissue organogenesis and regeneration provide perspectives on squamous cell cancers and adenocarcinomas in each tissue.
September 2018: Trends in Cell Biology
Emanuel Rognoni, Fiona M Watt
Skin architecture and function depend on diverse populations of epidermal cells and dermal fibroblasts. Reciprocal communication between the epidermis and dermis plays a key role in skin development, homeostasis and repair. While several stem cell populations have been identified in the epidermis with distinct locations and functions, it is now recognised that there is additional heterogeneity within the mesenchymal cells of the dermis. Here, we discuss recent insights into how these distinct cell populations are maintained and coordinated during development, homeostasis, and wound healing...
September 2018: Trends in Cell Biology
Bruce L Goode, Meredith O Sweeney, Julian A Eskin
Glia maturation factor (GMF) has recently been established as a regulator of the actin cytoskeleton with a unique role in remodeling actin network architecture. Conserved from yeast to mammals, GMF is one of five members of the ADF-H family of actin regulatory proteins, which includes ADF/cofilin, Abp1/Drebrin, Twinfilin, and Coactosin. GMF does not bind actin, but instead binds the Arp2/3 complex with high affinity. Through this association, GMF catalyzes the debranching of actin filament networks and inhibits actin nucleation by Arp2/3 complex...
September 2018: Trends in Cell Biology
Cynthia J Sieben, Ines Sturmlechner, Bart van de Sluis, Jan M van Deursen
Damaged cells at risk of neoplastic transformation can be neutralized by apoptosis or engagement of the senescence program, which induces permanent cell-cycle arrest and a bioactive secretome that is implicated in tumor immunosurveillance. While from an evolutionary perspective senescence is beneficial in that it protects against malignancies, the accumulation of senescent cells in tissues and organs with aging and at sites of various pathologies is largely detrimental. Because induction of senescence in cancer cells is emerging as a therapeutic concept, it will be important to consider these detrimental effects, including tumor-promoting properties that may drive the formation of secondary tumors or cancer relapse...
September 2018: Trends in Cell Biology
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