scholarly journals Dropping in on lipid droplets: insights into cellular stress and cancer

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Peter Shyu ◽  
Xing Fah Alex Wong ◽  
Karen Crasta ◽  
Guillaume Thibault
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Lipid Droplets ◽  
Cellular Stress ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Major Topic ◽  
Cellular Processes ◽  
Storage Studies ◽  
Cytoplasmic Structures

Lipid droplets (LD) have increasingly become a major topic of research in recent years following its establishment as a highly dynamic organelle. Contrary to the initial view of LDs being passive cytoplasmic structures for lipid storage, studies have provided support on how they act in concert with different organelles to exert functions in various cellular processes. Although lipid dysregulation resulting from aberrant LD homeostasis has been well characterised, how this translates and contributes to cancer progression is poorly understood. This review summarises the different paradigms on how LDs function in the regulation of cellular stress as a contributing factor to cancer progression. Mechanisms employed by a broad range of cancer cell types in differentially utilising LDs for tumourigenesis will also be highlighted. Finally, we discuss the potential of targeting LDs in the context of cancer therapeutics.

scholarly journals The transcriptional hallmarks of intra-tumor heterogeneity across a thousand tumors

2021 ◽  
Author(s):  
Avishai Gavish ◽  
Michael Tyler ◽  
Dor Simkin ◽  
Daniel Kovarsky ◽  
L. Nicolas Gonzalez Castro ◽  
...  
Keyword(s):  
Tumor Heterogeneity ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Cancer Type ◽  
Malignant Cells ◽  
Cellular Processes ◽  
Narrow View ◽  
Cancer Types ◽  
Context Specific ◽  
Tumor Types

Each tumor contains malignant cells that differ in genotype, phenotype, and in their interactions with the tumor micro-environment (TME). This results in distinct integrated cellular states that govern intra-tumor heterogeneity (ITH), a central challenge of cancer therapeutics. Dozens of recent studies have begun to describe ITH by single cell RNA-seq, but each study typically profiledonly a small number of tumors and provided a narrow view of transcriptional ITH. Here, we curate, annotate and integrate the data from 77 different studies to reveal the patterns of ITH across 1,163 tumor samples covering 24 tumor types. Focusing on the malignant cells, we find thousands of transcriptional ITH programs that can be described by 41 consensus meta-programs (MPs), each consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many different tumors. The MPs cover diverse cellular processes and differ in their cancer-type distribution. General MPs associated with processes such as cell cycle and stress vary within most tumors, while context-specific MPs reflect the unique biology of particular cancer types, often resembling developmental cell types and suggesting the co-existence of variable differentiation states within tumors. Some of the MPs are further associated with overall tumor proliferation or immune state, highlighting their potential clinical significance. Based on functional similarities among MPs, we propose a set of 11 hallmarks that together account for the majority of observed ITH programs. Given the breadth and scope of the investigated cohort, the MPs and hallmarks described here reflect the first comprehensive pan-cancer description of transcriptional ITH.

scholarly journals FOXA1 defines cancer cell specificity

2016 ◽  
Vol 2 (3) ◽  
pp. e1501473 ◽  
Author(s):  
Gaihua Zhang ◽  
Yongbing Zhao ◽  
Yi Liu ◽  
Li-Pin Kao ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Target Genes ◽  
Human Cancer ◽  
Cell Types ◽  
Human Cancer Cell Lines ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Pioneer Transcription Factor ◽  
Specific Regulation

A transcription factor functions differentially and/or identically in multiple cell types. However, the mechanism for cell-specific regulation of a transcription factor remains to be elucidated. We address how a single transcription factor, forkhead box protein A1 (FOXA1), forms cell-specific genomic signatures and differentially regulates gene expression in four human cancer cell lines (HepG2, LNCaP, MCF7, and T47D). FOXA1 is a pioneer transcription factor in organogenesis and cancer progression. Genomewide mapping of FOXA1 by chromatin immunoprecipitation sequencing annotates that target genes associated with FOXA1 binding are mostly common to these cancer cells. However, most of the functional FOXA1 target genes are specific to each cancer cell type. Further investigations using CRISPR-Cas9 genome editing technology indicate that cell-specific FOXA1 regulation is attributable to unique FOXA1 binding, genetic variations, and/or potential epigenetic regulation. Thus, FOXA1 controls the specificity of cancer cell types. We raise a “flower-blooming” hypothesis for cell-specific transcriptional regulation based on these observations.

scholarly journals Role of the Exosome in Ovarian Cancer Progression and Its Potential as a Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1147 ◽  
Author(s):  
Koji Nakamura ◽  
Kenjiro Sawada ◽  
Masaki Kobayashi ◽  
Mayuko Miyamoto ◽  
Aasa Shimizu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Peritoneal Dissemination ◽  
Cancer Therapeutics ◽  
Cell Types ◽  
Target Cells ◽  
Distinct Form ◽  
Cargo Delivery ◽  
Different Cell Types

Peritoneal dissemination is a distinct form of metastasis in ovarian cancer that precedes hematogenic or lymphatic metastasis. Exosomes are extracellular vesicles of 30–150 nm in diameter secreted by different cell types and internalized by target cells. There is emerging evidence that exosomes facilitate the peritoneal dissemination of ovarian cancer by mediating intercellular communication between cancer cells and the tumor microenvironment through the transfer of nucleic acids, proteins, and lipids. Furthermore, therapeutic applications of exosomes as drug cargo delivery are attracting research interest because exosomes are stabilized in circulation. This review highlights the functions of exosomes in each process of the peritoneal dissemination of ovarian cancer and discusses their potential for cancer therapeutics.

scholarly journals Extracellular Matrix Influencing HGF/c-MET Signaling Pathway: Impact on Cancer Progression

2018 ◽  
Vol 19 (11) ◽  
pp. 3300 ◽  
Author(s):  
Heydi Noriega-Guerra ◽  
Vanessa Freitas
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cell Communication ◽  
Dynamic Network ◽  
Cell Types ◽  
Bioactive Molecules ◽  
Matricellular Proteins ◽  
Cellular Processes

The extracellular matrix (ECM) is a crucial component of the tumor microenvironment involved in numerous cellular processes that contribute to cancer progression. It is acknowledged that tumor–stromal cell communication is driven by a complex and dynamic network of cytokines, growth factors and proteases. Thus, the ECM works as a reservoir for bioactive molecules that modulate tumor cell behavior. The hepatocyte growth factor (HGF) produced by tumor and stromal cells acts as a multifunctional cytokine and activates the c-MET receptor, which is expressed in different tumor cell types. The HGF/c-MET signaling pathway is associated with several cellular processes, such as proliferation, survival, motility, angiogenesis, invasion and metastasis. Moreover, c-MET activation can be promoted by several ECM components, including proteoglycans and glycoproteins that act as bridging molecules and/or signal co-receptors. In contrast, c-MET activation can be inhibited by proteoglycans, matricellular proteins and/or proteases that bind and sequester HGF away from the cell surface. Therefore, understanding the effects of ECM components on HGF and c-MET may provide opportunities for novel therapeutic strategies. Here, we give a short overview of how certain ECM components regulate the distribution and activation of HGF and c-MET.

scholarly journals Exosomes in cancer: small vesicular transporters for cancer progression and metastasis, biomarkers in cancer therapeutics

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4763 ◽  
Author(s):  
Atefe Abak ◽  
Alireza Abhari ◽  
Sevda Rahimzadeh
Keyword(s):  
Cancer Progression ◽  
Human Cancer ◽  
Cancer Therapeutics ◽  
Donor Cell ◽  
Cell Types ◽  
Bilayer Membrane ◽  
Phospholipid Bilayer ◽  
Bioactive Molecules ◽  
Target Cells ◽  
Phospholipid Bilayer Membrane

Cancer progression is a polygenic procedure in which the exosomes can function as substantial roles. Exosomes are tiny, phospholipid bilayer membrane nanovesicles of endocytic derivation with a diameter of 40–100 nm. These nanovesicles can transport bioactive molecules containing mRNAs, proteins, DNA fragments, and non-coding RNAs from a donor cell to recipient cells, and cause the alteration in genetic and epigenetic factors and reprogramming of the target cells. Many diverse cell types such as mesenchymal cells, immune cells, and cancer cells can induce the release of exosomes. Increasing evidence illustrated that the exosomes derived from tumor cells might trigger the tumor initiation, tumor cell growth and progression, metastasis, and drug resistance. The secreted nanovesicles of exosomes can play significant roles in cells communicate via shuttling the nucleic acid molecules and proteins to target cells and tissues. In this review, we discussed multiple mechanisms related to biogenesis, load, and shuttle of the exosomes. Also, we illustrated the diverse roles of exosomes in several types of human cancer development, tumor immunology, angiogenesis, and metastasis. The exosomes may act as the promising biomarkers for the prognosis of various types of cancers which suggested a new pathway for anti-tumor therapeutic of these nanovesicles and promoted exosome-based cancer for clinical diagnostic and remedial procedures.

scholarly journals STIM and ORAI proteins: crucial roles in hallmarks of cancer

2016 ◽  
Vol 310 (7) ◽  
pp. C509-C519 ◽  
Author(s):  
A. Fiorio Pla ◽  
K. Kondratska ◽  
N. Prevarskaya
Keyword(s):  
Cancer Progression ◽  
Cancer Therapeutics ◽  
Cellular Functions ◽  
Hallmarks Of Cancer ◽  
Cellular Processes ◽  
Store Depletion ◽  
Multistep Process ◽  
Intracellular Ca ◽  
Critical Components

Intracellular Ca2+ signals play a central role in several cellular processes; therefore it is not surprising that altered Ca2+ homeostasis regulatory mechanisms lead to a variety of severe pathologies, including cancer. Stromal interaction molecules (STIM) and ORAI proteins have been identified as critical components of Ca2+ entry in both store-dependent (SOCE mechanism) and independent by intracellular store depletion and have been implicated in several cellular functions. In recent years, both STIMs and ORAIs have emerged as possible molecular targets for cancer therapeutics. In this review we focus on the role of STIM and ORAI proteins in cancer progression. In particular we analyze their role in the different hallmarks of cancer, which represent the organizing principle that describes the complex multistep process of neoplastic diseases.

scholarly journals New monoclonal antibodies that recognize an unglycosylated, conserved, extracellular region of CD44 in vitro and in vivo, and can block tumorigenesis

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250175
Author(s):  
Daniel F. Lusche ◽  
Deborah J. Wessels ◽  
Ryan J. Reis ◽  
Cristopher C. Forrest ◽  
Alexis R. Thumann ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Cancer Cell ◽  
Cell Types ◽  
Western Blots ◽  
Cd44 Isoforms ◽  
Cellular Processes ◽  
Transmembrane Glycoprotein ◽  
Extracellular Region

CD44 is a transmembrane glycoprotein that binds to hyaluronic acid, plays roles in a number of cellular processes and is expressed in a variety of cell types. It is up-regulated in stem cells and cancer. Anti-CD44 monoclonal antibodies affect cell motility and aggregation, and repress tumorigenesis and metastasis. Here we describe four new anti-CD44 monoclonal antibodies originating from B cells of a mouse injected with a plasmid expressing CD44 isoform 12. The four monoclonal antibodies bind to the terminal, extracellular, conserved domain of CD44 isoforms. Based on differences in western blot patterns of cancer cell lysates, the four anti-CD44 mAbs separated into three distinct categories that include P4G9, P3D2, and P3A7, and P3G4. Spot assay analysis with peptides generated inEscherichia colisupport the conclusion that the monoclonal antibodies recognize unglycosylated sequences in the N-terminal conserved region between amino acid 21–220, and analyses with a peptide generated in human embryonic kidney 293 cells, demonstrate that these monoclonal antibodies bind to these peptides only after deglycosylation. Western blots with lysates from three cancer cell lines demonstrate that several CD44 isoforms are unglycosylated in the anti-CD44 target regions. The potential utility of the monoclonal antibodies in blocking tumorigenesis was tested by co-injection of cells of the breast cancer-derived tumorigenic cell line MDA-MB-231 with the anti-CD44 monoclonal antibody P3D2 into the mammary fat pads of mice. All five control mice injected with MDA-MB-231 cells plus anti-IgG formed palpable tumors, while only one of the six test mice injected with MDA-MB-231 cells plus P3D2 formed a tiny tumor, while the remaining five were tumor-free, indicating that the four anti-CD44 mAbs may be useful therapeutically.

scholarly journals Mechanobiological Implications of Cancer Progression in Space

2021 ◽  
Vol 9 ◽  
Author(s):  
Hyondeog Kim ◽  
Yun Shin ◽  
Dong-Hwee Kim
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cellular Response ◽  
Cell Types ◽  
Space Environment ◽  
Space Biology ◽  
Terrestrial Environment ◽  
Actual Space

The human body is normally adapted to maintain homeostasis in a terrestrial environment. The novel conditions of a space environment introduce challenges that changes the cellular response to its surroundings. Such an alteration causes physical changes in the extracellular microenvironment, inducing the secretion of cytokines such as interleukin-6 (IL-6) and tumor growth factor-β (TGF-β) from cancer cells to enhance cancer malignancy. Cancer is one of the most prominent cell types to be affected by mechanical cues via active interaction with the tumor microenvironment. However, the mechanism by which cancer cells mechanotransduce in the space environment, as well as the influence of this process on human health, have not been fully elucidated. Due to the growing interest in space biology, this article reviews cancer cell responses to the representative conditions altered in space: microgravity, decompression, and irradiation. Interestingly, cytokine and gene expression that assist in tumor survival, invasive phenotypic transformation, and cancer cell proliferation are upregulated when exposed to both simulated and actual space conditions. The necessity of further research on space mechanobiology such as simulating more complex in vivo experiments or finding other mechanical cues that may be encountered during spaceflight are emphasized.

scholarly journals The “Janus Face” of Platelets in Cancer

2020 ◽  
Vol 21 (3) ◽  
pp. 788 ◽  
Author(s):  
Maria Valeria Catani ◽  
Isabella Savini ◽  
Valentina Tullio ◽  
Valeria Gasperi
Keyword(s):  
Cancer Cell ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Cell Types ◽  
Vital Role ◽  
Bioactive Molecules ◽  
Cancer Type ◽  
Cancer Management ◽  
The Impact

Besides their vital role in hemostasis and thrombosis, platelets are also recognized to be involved in cancer, where they play an unexpected central role: They actively influence cancer cell behavior, but, on the other hand, platelet physiology and phenotype are impacted by tumor cells. The existence of this platelet-cancer loop is supported by a large number of experimental and human studies reporting an association between alterations in platelet number and functions and cancer, often in a way dependent on patient, cancer type and treatment. Herein, we shall report on an update on platelet-cancer relationships, with a particular emphasis on how platelets might exert either a protective or a deleterious action in all steps of cancer progression. To this end, we will describe the impact of (i) platelet count, (ii) bioactive molecules secreted upon platelet activation, and (iii) microvesicle-derived miRNAs on cancer behavior. Potential explanations of conflicting results are also reported: Both intrinsic (heterogeneity in platelet-derived bioactive molecules with either inhibitory or stimulatory properties; features of cancer cell types, such as aggressiveness and/or tumour stage) and extrinsic (heterogeneous characteristics of cancer patients, study design and sample preparation) factors, together with other confounding elements, contribute to “the Janus face” of platelets in cancer. Given the difficulty to establish the univocal role of platelets in a tumor, a better understanding of their exact contribution is warranted, in order to identify an efficient therapeutic strategy for cancer management, as well as for better prevention, screening and risk assessment protocols.

scholarly journals Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 480
Author(s):  
Anastasia S. Frolova ◽  
Anastasiia I. Petushkova ◽  
Vladimir A. Makarov ◽  
Surinder M. Soond ◽  
Andrey A. Zamyatnin
Keyword(s):  
Matrix Metalloproteinases ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Nuclear Matrix ◽  
Nuclear Translocation ◽  
Cell Types ◽  
Cellular Growth ◽  
Cellular Processes ◽  
Wide Range ◽  
Cellular Apoptosis

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for the degradation of a wide range of extracellular matrix proteins, which are involved in many cellular processes to ensure the normal development of tissues and organs. Overexpression of MMPs has been observed to facilitate cellular growth, migration, and metastasis of tumor cells during cancer progression. A growing number of these proteins are being found to exist in the nuclei of both healthy and tumor cells, thus highlighting their localization as having a genuine purpose in cellular homeostasis. The mechanism underlying nuclear transport and the effects of MMP nuclear translocation have not yet been fully elucidated. To date, nuclear MMPs appear to have a unique impact on cellular apoptosis and gene regulation, which can have effects on immune response and tumor progression, and thus present themselves as potential therapeutic targets in certain types of cancer or disease. Herein, we highlight and evaluate what progress has been made in this area of research, which clearly has some value as a specific and unique way of targeting the activity of nuclear matrix metalloproteinases within various cell types.

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