scholarly journals Four faces of cellular senescence

2011 ◽  
Vol 192 (4) ◽  
pp. 547-556 ◽  
Author(s):  
Francis Rodier ◽  
Judith Campisi
Keyword(s):  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cellular Senescence ◽  
Tumor Suppression ◽  
Tissue Repair ◽  
Tumor Promotion ◽  
Biological Processes ◽  
Opposing Effects ◽  
Potential Cancer

Cellular senescence is an important mechanism for preventing the proliferation of potential cancer cells. Recently, however, it has become apparent that this process entails more than a simple cessation of cell growth. In addition to suppressing tumorigenesis, cellular senescence might also promote tissue repair and fuel inflammation associated with aging and cancer progression. Thus, cellular senescence might participate in four complex biological processes (tumor suppression, tumor promotion, aging, and tissue repair), some of which have apparently opposing effects. The challenge now is to understand the senescence response well enough to harness its benefits while suppressing its drawbacks.

scholarly journals Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics

2020 ◽  
Vol 21 (9) ◽  
pp. 3100 ◽  
Author(s):  
Alia Ghoneum ◽  
Ammar Yasser Abdulfattah ◽  
Bailey Olivia Warren ◽  
Junjun Shu ◽  
Neveen Said
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Metabolic Pathways ◽  
Redox Homeostasis ◽  
Ros Production ◽  
Biological Processes ◽  
Survival Pathways ◽  
Oncogenic Mutations ◽  
And Oxidative Stress ◽  
Shed Light

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.

scholarly journals Ribosome Biogenesis Alterations in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2361
Author(s):  
Sophie Nait Slimane ◽  
Virginie Marcel ◽  
Tanguy Fenouil ◽  
Frédéric Catez ◽  
Jean-Christophe Saurin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Synthesis ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Predictive Biomarkers ◽  
Cancer Cell Growth ◽  
Therapeutic Drugs ◽  
Key Driver

Many studies have focused on understanding the regulation and functions of aberrant protein synthesis in colorectal cancer (CRC), leaving the ribosome, its main effector, relatively underappreciated in CRC. The production of functional ribosomes is initiated in the nucleolus, requires coordinated ribosomal RNA (rRNA) processing and ribosomal protein (RP) assembly, and is frequently hyperactivated to support the needs in protein synthesis essential to withstand unremitting cancer cell growth. This elevated ribosome production in cancer cells includes a strong alteration of ribosome biogenesis homeostasis that represents one of the hallmarks of cancer cells. None of the ribosome production steps escape this cancer-specific dysregulation. This review summarizes the early and late steps of ribosome biogenesis dysregulations described in CRC cell lines, intestinal organoids, CRC stem cells and mouse models, and their possible clinical implications. We highlight how this cancer-related ribosome biogenesis, both at quantitative and qualitative levels, can lead to the synthesis of ribosomes favoring the translation of mRNAs encoding hyperproliferative and survival factors. We also discuss whether cancer-related ribosome biogenesis is a mere consequence of cancer progression or is a causal factor in CRC, and how altered ribosome biogenesis pathways can represent effective targets to kill CRC cells. The association between exacerbated CRC cell growth and alteration of specific steps of ribosome biogenesis is highlighted as a key driver of tumorigenesis, providing promising perspectives for the implementation of predictive biomarkers and the development of new therapeutic drugs.

scholarly journals Emergence of Cancer-Associated Fibroblasts as an Indispensable Cellular Player in Bone Metastasis Process

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2896
Author(s):  
Naofumi Mukaida ◽  
Di Zhang ◽  
So-ichiro Sasaki
Keyword(s):  
Bone Marrow ◽  
Bone Metastasis ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Growth ◽  
Lung Cancers ◽  
Osteoclast Activation

Bone metastasis is frequently complicated in patients with advanced solid cancers such as breast, prostate and lung cancers, and impairs patients’ quality of life and prognosis. At the first step of bone metastasis, cancer cells adhere to the endothelium in bone marrow and survive in a dormant state by utilizing hematopoietic niches present therein. Once a dormant stage is disturbed, cancer cells grow through the interaction with various bone marrow resident cells, particularly osteoclasts and osteoblasts. Consequently, osteoclast activation is a hallmark of bone metastasis. As a consequence, the drugs targeting osteoclast activation are frequently used to treat bone metastasis but are not effective to inhibit cancer cell growth in bone marrow. Thus, additional types of resident cells are presumed to contribute to cancer cell growth in bone metastasis sites. Cancer-associated fibroblasts (CAFs) are fibroblasts that accumulate in cancer tissues and can have diverse roles in cancer progression and metastasis. Given the presence of CAFs in bone metastasis sites, CAFs are emerging as an important cellular player in bone metastasis. Hence, in this review, we will discuss the potential roles of CAFs in tumor progression, particularly bone metastasis.

scholarly journals Cellular Senescence limits Translational Readthrough

Biology Open ◽  
2021 ◽  
Author(s):  
Neylen del Toro ◽  
Frédéric Lessard ◽  
Jacob Bouchard ◽  
Nasrin Mobasheri ◽  
Jordan Guillon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cellular Senescence ◽  
Tumor Suppressors ◽  
Cancer Biology ◽  
Translation Termination ◽  
Origin And Evolution ◽  
Dna Mutations ◽  
Translational Readthrough

The origin and evolution of cancer cells is considered to be mainly fueled by DNA mutations. Although translation errors could also expand the cellular proteome, their role in cancer biology remains poorly understood. Tumor suppressors called caretakers block cancer initiation and progression by preventing DNA mutations and/or stimulating DNA repair. If translational errors contribute to tumorigenesis, then caretakers genes should prevent such errors in normal cells in response to oncogenic stimuli. Here, we show that the process of cellular senescence induced by oncogenes, tumor suppressors or chemotherapeutic drugs is associated to a reduction in translational readthrough (TR) measured using reporters containing termination codons withing the context of both normal translation termination or programmed TR. Senescence reduced both basal TR and TR stimulated by aminoglycosides. Mechanistically, the reduction of TR during senescence is controlled by the RB tumor suppressor pathway. Cells that escape from cellular senescence either induced by oncogenes or chemotherapy have an increased TR. Also, breast cancer cells that escape from therapy-induced senescence express high levels of AGO1x, a TR isoform of AGO1 linked to breast cancer progression. We propose that senescence and the RB pathway reduce TR limiting proteome diversity and the expression of TR proteins required for cancer cell proliferation.

scholarly journals Methionine Supplementation Affects Metabolism and Reduces Tumor Aggressiveness in Liver Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2491
Author(s):  
Farida Tripodi ◽  
Beatrice Badone ◽  
Marta Vescovi ◽  
Riccardo Milanesi ◽  
Simona Nonnis ◽  
...  
Keyword(s):  
Cell Growth ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Tca Cycle ◽  
Central Carbon Metabolism ◽  
Main Role ◽  
Atp Production ◽  
Liver Cancer Cells ◽  
Methionine Supplementation

Liver cancer is one of the most common cancer worldwide with a high mortality. Methionine is an essential amino acid required for normal development and cell growth, is mainly metabolized in the liver, and its role as an anti-cancer supplement is still controversial. Here, we evaluate the effects of methionine supplementation in liver cancer cells. An integrative proteomic and metabolomic analysis indicates a rewiring of the central carbon metabolism, with an upregulation of the tricarboxylic acid (TCA) cycle and mitochondrial adenosine triphosphate (ATP) production in the presence of high methionine and AMP-activated protein kinase (AMPK) inhibition. Methionine supplementation also reduces growth rate in liver cancer cells and induces the activation of both the AMPK and mTOR pathways. Interestingly, in high methionine concentration, inhibition of AMPK strongly impairs cell growth, cell migration, and colony formation, indicating the main role of AMPK in the control of liver cancer phenotypes. Therefore, regulation of methionine in the diet combined with AMPK inhibition could reduce liver cancer progression.

scholarly journals CRSP8 promotes thyroid cancer progression by antagonizing IKKα-induced cell differentiation

2020 ◽  
Author(s):  
Yina Liao ◽  
Yijun Hua ◽  
Yizhuo Li ◽  
Changlin Zhang ◽  
Wendan Yu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Direct Interaction ◽  
Anaplastic Thyroid Cancer ◽  
Human Thyroid ◽  
Induced Apoptosis ◽  
Thyroid Cancer Cells

Abstract CRSP8 plays an important role in recruiting mediators to genes through direct interaction with various DNA-bound transactivators. In this study, we uncovered the unique function of CRSP8 in suppressing thyroid cancer differentiation and promoting thyroid cancer progression via targeting IKKα signaling. CRSP8 was highly expressed in human thyroid cancer cells and tissues, especially in anaplastic thyroid cancer (ATC). Knockdown of CRSP8 suppressed cell growth, migration, invasion, stemness, and induced apoptosis and differentiation in ATC cells, while its overexpression displayed opposite effects in differentiated thyroid cancer (DTC) cells. Mechanistically, CRSP8 downregulated IKKα expression by binding to the IKKα promoter region (−257 to −143) to negatively regulate its transcription. Knockdown or overexpression of IKKα significantly reversed the expression changes of the differentiation and EMT-related markers and cell growth changes mediated by CRSP8 knockdown or overexpression in ATC or DTC cells. The in vivo study also validated that CRSP8 knockdown inhibited the growth of thyroid cancer by upregulating IKKα signaling in a mouse model of human ATC. Furthermore, we found that CRSP8 regulated the sensitivity of thyroid cancer cells to chemotherapeutics, including cisplatin and epirubicin. Collectively, our results demonstrated that CRSP8 functioned as a modulator of IKKα signaling and a suppressor of thyroid cancer differentiation, suggesting a potential therapeutic strategy for ATC by targeting CRSP8/IKKα pathway.

scholarly journals The Identification of RNA-Binding Proteins Functionally Associated with Tumor Progression in Gastrointestinal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3165
Author(s):  
Hiroaki Konishi ◽  
Shin Kashima ◽  
Takuma Goto ◽  
Katsuyoshi Ando ◽  
Aki Sakatani ◽  
...  
Keyword(s):  
Cell Growth ◽  
Mrna Expression ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Functional Screening ◽  
Aberrant Expression ◽  
Sirna Library

Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.

Physiological and pathological relevance of secretory microRNAs and a perspective on their clinical application

2014 ◽  
Vol 395 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Takeshi Katsuda ◽  
Shingo Ikeda ◽  
Yusuke Yoshioka ◽  
Nobuyoshi Kosaka ◽  
Masaki Kawamata ◽  
...  
Keyword(s):  
Clinical Application ◽  
Cancer Progression ◽  
Immune Regulation ◽  
Tissue Repair ◽  
Cell Types ◽  
Clinical Applications ◽  
Research Field ◽  
Biological Processes ◽  
Exosomal Mirnas ◽  
Significant Attention

Abstract MicroRNAs (miRNAs) have attracted significant attention because of their important roles in a variety of physiological and pathological processes. Recent studies have shown that many cell types secrete miRNAs by packaging them into lipid-bilayered small vesicles called exosomes. Furthermore, exosomal miRNAs travel between cells, exert their RNAi effects in the recipient cells, and play important roles in various biological processes. In this article, we will summarize and describe the latest studies on exosomal miRNAs by focusing on their roles in cancer progression, immune regulation, and tissue repair. We will also provide a perspective on the clinical applications of this research field.

scholarly journals Beta 2 Adrenergic Receptor Antagonist Propranolol and Opioidergic Receptor Antagonist Naltrexone Produce Synergistic Effects on Breast Cancer Growth Prevention by Acting on Cancer Cells and Immune Environment in a Preclinical Model of Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4858
Author(s):  
Sengottuvelan Murugan ◽  
Bénédicte Rousseau ◽  
Dipak K. Sarkar
Keyword(s):  
Breast Cancer ◽  
Cell Growth ◽  
Receptor Antagonist ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Synergistic Effects ◽  
Treatment Modalities ◽  
Preclinical Model ◽  
Antitumor Effects ◽  
Mesenchymal Transition

Cancer progression is known to be promoted by increased body stress caused by elevated beta-adrenergic and opioidergic nervous system activities. The effects of β2-adrenergic blocker propranolol (PRO) and μ-opioid receptor antagonist naltrexone (NTX) were tested using a preclinical model of human breast cancer. These drugs, individually, and more potently when combined, inhibited the cell growth and progression of breast cancer cells in vitro in cultures, and in vivo in rat xenografts. The antitumor activities of these drugs were associated with direct cell intrinsic effects, including increased cell growth arrest, elevated levels of apoptotic proteins, and reduced production of epithelial–mesenchymal transition factors by the tumor cells, as well as effects on innate immune activation and reduced inflammatory cytokine levels in plasma. These data suggest that the combined treatments of PRO and NTX produce impressive antitumor effects in the preclinical breast cancer model, and thereby may provide a new combinatorial treatment strategy with more clinical treatment modalities.

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