scholarly journals Ferroptosis Meets Cell–Cell Contacts

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2462
Author(s):  
Cornelia Dietrich ◽  
Thomas G. Hofmann
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Types ◽  
Therapy Resistance ◽  
Cell Contacts ◽  
Molecular Events ◽  
Underlying Mechanisms ◽  
Context Specific ◽  
Cell Cell

Ferroptosis is a regulated form of cell death characterized by iron dependency and increased lipid peroxidation. Initially assumed to be selectively induced in tumour cells, there is increasing evidence that ferroptosis plays an important role in pathophysiology and numerous cell types and tissues. Deregulated ferroptosis has been linked to human diseases, such as neurodegenerative diseases, cardiovascular disorders, and cancer. Along these lines, ferroptosis is a promising pathway to overcoming therapy resistance of cancer cells. It is therefore of utmost importance to understand the cellular signalling pathways and the molecular mechanisms underlying ferroptosis regulation, including context-specific effects mediated by the neighbouring cells through cell–cell contacts. Here, we give an overview on the molecular events and machinery linked to ferroptosis induction and commitment. We further summarize and discuss current knowledge about the role of cell–cell contacts, which differ in ferroptosis regulation between normal somatic cells and cancer cells. We present emerging concepts on the underlying mechanisms, address open questions, and discuss the possible impact of cell–cell contacts on exploiting ferroptosis in cancer therapy.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

The cancer cell adhesion resistome: mechanisms, targeting and translational approaches

2017 ◽  
Vol 398 (7) ◽  
pp. 721-735 ◽  
Author(s):  
Ellen Dickreuter ◽  
Nils Cordes
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Adapter Proteins ◽  
Cancer Therapies ◽  
Synthetic Lethal ◽  
Cancer Cell Adhesion ◽  
Underlying Mechanisms ◽  
Preclinical Work

Abstract Cell adhesion-mediated resistance limits the success of cancer therapies and is a great obstacle to overcome in the clinic. Since the 1990s, where it became clear that adhesion of tumor cells to the extracellular matrix is an important mediator of therapy resistance, a lot of work has been conducted to understand the fundamental underlying mechanisms and two paradigms were deduced: cell adhesion-mediated radioresistance (CAM-RR) and cell adhesion-mediated drug resistance (CAM-DR). Preclinical work has evidently demonstrated that targeting of integrins, adapter proteins and associated kinases comprising the cell adhesion resistome is a promising strategy to sensitize cancer cells to both radiotherapy and chemotherapy. Moreover, the cell adhesion resistome fundamentally contributes to adaptation mechanisms induced by radiochemotherapy as well as molecular drugs to secure a balanced homeostasis of cancer cells for survival and growth. Intriguingly, this phenomenon provides a basis for synthetic lethal targeted therapies simultaneously administered to standard radiochemotherapy. In this review, we summarize current knowledge about the cell adhesion resistome and highlight targeting strategies to override CAM-RR and CAM-DR.

Cancer-associated fibroblasts (CAFs) in thyroid papillary carcinoma: molecular networks and interactions

2021 ◽  
pp. jclinpath-2020-207357
Author(s):  
Jeehoon Ham ◽  
Bin Wang ◽  
Joseph William Po ◽  
Amandeep Singh ◽  
Navin Niles ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Molecular Networks ◽  
Cancer Cell Growth ◽  
Molecular Events

In 1989, Stephen Paget proposed the ‘seed and soil’ theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.

scholarly journals The Role of Cancer-Associated Fibroblasts in Prostate Cancer Tumorigenesis

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1887 ◽  
Author(s):  
Francesco Bonollo ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Sofia Karkampouna
Keyword(s):  
Prostate Cancer ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Progression ◽  
Normal Prostate ◽  
Prostate Tumorigenesis

Tumors strongly depend on their surrounding tumor microenvironment (TME) for growth and progression, since stromal elements are required to generate the optimal conditions for cancer cell proliferation, invasion, and possibly metastasis. Prostate cancer (PCa), though easily curable during primary stages, represents a clinical challenge in advanced stages because of the acquisition of resistance to anti-cancer treatments, especially androgen-deprivation therapies (ADT), which possibly lead to uncurable metastases such as those affecting the bone. An increasing number of studies is giving evidence that prostate TME components, especially cancer-associated fibroblasts (CAFs), which are the most abundant cell type, play a causal role in PCa since the very early disease stages, influencing therapy resistance and metastatic progression. This is highlighted by the prognostic value of the analysis of stromal markers, which may predict disease recurrence and metastasis. However, further investigations on the molecular mechanisms of tumor–stroma interactions are still needed to develop novel therapeutic approaches targeting stromal components. In this review, we report the current knowledge of the characteristics and functions of the stroma in prostate tumorigenesis, including relevant discussion of normal prostate homeostasis, chronic inflammatory conditions, pre-neoplastic lesions, and primary and metastatic tumors. Specifically, we focus on the role of CAFs, to point out their prognostic and therapeutic potential in PCa.

scholarly journals Classical cadherins control nucleus and centrosome position and cell polarity

2009 ◽  
Vol 185 (5) ◽  
pp. 779-786 ◽  
Author(s):  
Isabelle Dupin ◽  
Emeline Camand ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Polarity ◽  
Control Cell ◽  
Cell Types ◽  
Free Cell ◽  
Cell Polarization ◽  
Cell Interactions ◽  
Spatial Cues ◽  
Cell Contacts ◽  
Classical Cadherins ◽  
Cell Cell

Control of cell polarity is crucial during tissue morphogenesis and renewal, and depends on spatial cues provided by the extracellular environment. Using micropatterned substrates to impose reproducible cell–cell interactions, we show that in the absence of other polarizing cues, cell–cell contacts are the main regulator of nucleus and centrosome positioning, and intracellular polarized organization. In a variety of cell types, including astrocytes, epithelial cells, and endothelial cells, calcium-dependent cadherin-mediated cell–cell interactions induce nucleus and centrosome off-centering toward cell–cell contacts, and promote orientation of the nucleus–centrosome axis toward free cell edges. Nucleus and centrosome off-centering is controlled by N-cadherin through the regulation of cell interactions with the extracellular matrix, whereas the orientation of the nucleus–centrosome axis is determined by the geometry of N-cadherin–mediated contacts. Our results demonstrate that in addition to the specific function of E-cadherin in regulating baso-apical epithelial polarity, classical cadherins control cell polarization in otherwise nonpolarized cells.

scholarly journals Discover context-specific combinatorial transcription factor interactions by integrating diverse ChIP-Seq data sets

2013 ◽  
Vol 42 (4) ◽  
pp. e24-e24 ◽  
Author(s):  
Li Teng ◽  
Bing He ◽  
Peng Gao ◽  
Long Gao ◽  
Kai Tan
Keyword(s):  
Current Knowledge ◽  
Chromatin Modification ◽  
Cell Types ◽  
Fine Tuning ◽  
Joint Analysis ◽  
Data Types ◽  
Missed Opportunities ◽  
Combinatorial Regulation ◽  
Flexible Architecture ◽  
Context Specific

Abstract Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. Current knowledge about combinatorial regulation is rather limited due to the lack of suitable experimental technologies and bioinformatics tools. The rapid accumulation of ChIP-Seq data has provided genome-wide occupancy maps for a large number of TFs and chromatin modification marks for identifying enhancers without knowing individual TF binding sites. Integration of the two data types has not been researched extensively, resulting in underused data and missed opportunities. We describe a novel method for discovering frequent combinatorial occupancy patterns by multiple TFs at enhancers. Our method is based on probabilistic item set mining and takes into account uncertainty in both types of ChIP-Seq data. By joint analysis of 108 TFs in four human cell types, we found that cell–type-specific interactions among TFs are abundant and that the majority of enhancers have flexible architecture. We show that several families of transposable elements disproportionally overlap with enhancers with combinatorial patterns, suggesting that these transposable element families play an important role in the evolution of combinatorial regulation.

scholarly journals Characterization of primary cilia features reveal cell-type specific variability in in vitro models of osteogenic and chondrogenic differentiation

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9799
Author(s):  
Priyanka Upadhyai ◽  
Vishal Singh Guleria ◽  
Prajna Udupa
Keyword(s):  
Cell Lines ◽  
Chondrogenic Differentiation ◽  
Primary Cilia ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Cell Types ◽  
Treatment Modalities ◽  
Cell Type ◽  
Cell Type Specific

Primary cilia are non-motile sensory antennae present on most vertebrate cell surfaces. They serve to transduce and integrate diverse external stimuli into functional cellular responses vital for development, differentiation and homeostasis. Ciliary characteristics, such as length, structure and frequency are often tailored to distinct differentiated cell states. Primary cilia are present on a variety of skeletal cell-types and facilitate the assimilation of sensory cues to direct skeletal development and repair. However, there is limited knowledge of ciliary variation in response to the activation of distinct differentiation cascades in different skeletal cell-types. C3H10T1/2, MC3T3-E1 and ATDC5 cells are mesenchymal stem cells, preosteoblast and prechondrocyte cell-lines, respectively. They are commonly employed in numerous in vitro studies, investigating the molecular mechanisms underlying osteoblast and chondrocyte differentiation, skeletal disease and repair. Here we sought to evaluate the primary cilia length and frequencies during osteogenic differentiation in C3H10T1/2 and MC3T3-E1 and chondrogenic differentiation in ATDC5 cells, over a period of 21 days. Our data inform on the presence of stable cilia to orchestrate signaling and dynamic alterations in their features during extended periods of differentiation. Taken together with existing literature these findings reflect the occurrence of not only lineage but cell-type specific variation in ciliary attributes during differentiation. These results extend our current knowledge, shining light on the variabilities in primary cilia features correlated with distinct differentiated cell phenotypes. It may have broader implications in studies using these cell-lines to explore cilia dependent cellular processes and treatment modalities for skeletal disorders centered on cilia modulation.

scholarly journals Predicting global dynamics of spatial microbial communities from local interaction rules

2020 ◽  
Author(s):  
Simon van Vliet ◽  
Christoph Hauert ◽  
Martin Ackermann ◽  
Alma Dal Co
Keyword(s):  
Growth Rate ◽  
Microbial Communities ◽  
Molecular Mechanisms ◽  
Single Cells ◽  
Cell Types ◽  
Cell Interactions ◽  
Community Level ◽  
Global Dynamics ◽  
Mathematical Framework ◽  
Cell Cell

AbstractInteractions between cells drive biological processes across all of life, from microbes in the environment to cells in multicellular organisms. Interactions often arise in spatially structured settings, where cells mostly interact with their neighbors. A central question is how the properties of biological systems emerge from local interactions. This question is very relevant in the context of microbial communities, such as biofilms, where cells live close by in space and are connected via a dense network of biochemical interactions. To understand and control the functioning of these communities, it is essential to uncover how community-level properties, such as the community composition, spatial arrangement, and growth rate, arise from these interactions. Here, we develop a mathematical framework that can predict community-level properties from the molecular mechanisms underlying the cell-cell interactions for systems consisting of two cell types. Our predictions match quantitative measurements from an experimental cross-feeding community. For these cross-feeding communities, the community growth rate is reduced when cells interact only with few neighbors; as a result, some communities can co-exist in a well-mixed system, but not in a spatial one. In general, our framework shows that key molecular parameters underlying the cell-cell interactions (e.g. the uptake and leakage rates of molecules) determine community level properties. Our framework can be extended to a variety of systems of two interacting cell types, within and beyond the microbial world, and contributes to our understanding of how biological functions arise from interactions between single cells.

scholarly journals Molecular and Cellular Mechanisms Modulating Trained Immunity by Various Cell Types in Response to Pathogen Encounter

2021 ◽  
Vol 12 ◽  
Author(s):  
Orlando A. Acevedo ◽  
Roslye V. Berrios ◽  
Linmar Rodríguez-Guilarte ◽  
Bastián Lillo-Dapremont ◽  
Alexis M. Kalergis
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tca Cycle ◽  
Cell Types ◽  
Innate Immune ◽  
Epigenetic Changes ◽  
Cellular Mechanisms ◽  
Functional Changes ◽  
Trained Immunity

The induction of trained immunity represents an emerging concept defined as the ability of innate immune cells to acquire a memory phenotype, which is a typical hallmark of the adaptive response. Key points modulated during the establishment of trained immunity include epigenetic, metabolic and functional changes in different innate-immune and non-immune cells. Regarding to epigenetic changes, it has been described that long non-coding RNAs (LncRNAs) act as molecular scaffolds to allow the assembly of chromatin-remodeling complexes that catalyze epigenetic changes on chromatin. On the other hand, relevant metabolic changes that occur during this process include increased glycolytic rate and the accumulation of metabolites from the tricarboxylic acid (TCA) cycle, which subsequently regulate the activity of histone-modifying enzymes that ultimately drive epigenetic changes. Functional consequences of established trained immunity include enhanced cytokine production, increased antigen presentation and augmented antimicrobial responses. In this article, we will discuss the current knowledge regarding the ability of different cell subsets to acquire a trained immune phenotype and the molecular mechanisms involved in triggering such a response. This knowledge will be helpful for the development of broad-spectrum therapies against infectious diseases based on the modulation of epigenetic and metabolic cues regulating the development of trained immunity.

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