scholarly journals Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 791
Author(s):  
Qi Liu ◽  
Bayonle Aminu ◽  
Olivia Roscow ◽  
Wei Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Post Translational Modification ◽  
E3 Ligases ◽  
Tumor Microenvironments ◽  
Cellular Immune ◽  
Ubiquitin Conjugating Enzymes ◽  
Cellular Components

Tumor microenvironments are composed of a myriad of elements, both cellular (immune cells, cancer-associated fibroblasts, mesenchymal stem cells, etc.) and non-cellular (extracellular matrix, cytokines, growth factors, etc.), which collectively provide a permissive environment enabling tumor progression. In this review, we focused on the regulation of tumor microenvironment through ubiquitination. Ubiquitination is a reversible protein post-translational modification that regulates various key biological processes, whereby ubiquitin is attached to substrates through a catalytic cascade coordinated by multiple enzymes, including E1 ubiquitin-activating enzymes, E2 ubiquitin-conjugating enzymes and E3 ubiquitin ligases. In contrast, ubiquitin can be removed by deubiquitinases in the process of deubiquitination. Here, we discuss the roles of E3 ligases and deubiquitinases as modulators of both cellular and non-cellular components in tumor microenvironment, providing potential therapeutic targets for cancer therapy. Finally, we introduced several emerging technologies that can be utilized to develop effective therapeutic agents for targeting tumor microenvironment.

scholarly journals Structural Diversity of Ubiquitin E3 Ligase

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6682
Author(s):  
Sachiko Toma-Fukai ◽  
Toshiyuki Shimizu
Keyword(s):  
E3 Ligase ◽  
Structural Diversity ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
E3 Ligases ◽  
Cellular Processes ◽  
Ubiquitin E3 Ligase ◽  
Ubiquitin Ligase E3 ◽  
Ubiquitin Conjugating Enzyme

The post-translational modification of proteins regulates many biological processes. Their dysfunction relates to diseases. Ubiquitination is one of the post-translational modifications that target lysine residue and regulate many cellular processes. Three enzymes are required for achieving the ubiquitination reaction: ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). E3s play a pivotal role in selecting substrates. Many structural studies have been conducted to reveal the molecular mechanism of the ubiquitination reaction. Recently, the structure of PCAF_N, a newly categorized E3 ligase, was reported. We present a review of the recent progress toward the structural understanding of E3 ligases.

scholarly journals Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

2021 ◽  
Vol 9 ◽  
Author(s):  
Siyuan Luan ◽  
Xiaoxi Zeng ◽  
Chao Zhang ◽  
Jiajun Qiu ◽  
Yushang Yang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Esophageal Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Benefit ◽  
Therapeutic Agents ◽  
Development Of Resistance ◽  
Cellular Components

Drug resistance represents the major obstacle to get the maximum therapeutic benefit for patients with esophageal cancer since numerous patients are inherently or adaptively resistant to therapeutic agents. Notably, increasing evidence has demonstrated that drug resistance is closely related to the crosstalk between tumor cells and the tumor microenvironment (TME). TME is a dynamic and ever-changing complex biological network whose diverse cellular and non-cellular components influence hallmarks and fates of tumor cells from the outside, and this is responsible for the development of resistance to conventional therapeutic agents to some extent. Indeed, the formation of drug resistance in esophageal cancer should be considered as a multifactorial process involving not only cancer cells themselves but cancer stem cells, tumor-associated stromal cells, hypoxia, soluble factors, extracellular vesicles, etc. Accordingly, combination therapy targeting tumor cells and tumor-favorable microenvironment represents a promising strategy to address drug resistance and get better therapeutic responses for patients with esophageal cancer. In this review, we mainly focus our discussion on molecular mechanisms that underlie the role of TME in drug resistance in esophageal cancer. We also discuss the opportunities and challenges for therapeutically targeting tumor-favorable microenvironment, such as membrane proteins, pivotal signaling pathways, and cytokines, to attenuate drug resistance in esophageal cancer.

scholarly journals The Interplay of Autophagy and Tumor Microenvironment in Colorectal Cancer—Ways of Enhancing Immunotherapy Action

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 533 ◽  
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Georgia Kyriakopoulou ◽  
Athanasios G. Papavassiliou ◽  
Michalis V. Karamouzis
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Tumor Microenvironment ◽  
Tumor Stroma ◽  
Cellular Functions ◽  
Different Types ◽  
Cellular Immune ◽  
Cellular Components ◽  
Catabolic Process

Autophagy as a primary homeostatic and catabolic process is responsible for the degradation and recycling of proteins and cellular components. The mechanism of autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions, and resistance to cancer therapy. A growing body of evidence suggests that autophagy is also a key regulator of the tumor microenvironment and cellular immune response in different types of cancer, including colorectal cancer (CRC). Furthermore, autophagy is responsible for initiating the immune response especially when it precedes cell death. However, the role of autophagy in CRC and the tumor microenvironment remains controversial. In this review, we identify the role of autophagy in tumor microenvironment regulation and the specific mechanism by which autophagy is implicated in immune responses during CRC tumorigenesis and the context of anticancer therapy.

scholarly journals Quadruplex Ligands in Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3156
Author(s):  
Victoria Sanchez-Martin ◽  
Miguel Soriano ◽  
Jose Antonio Garcia-Salcedo
Keyword(s):  
Cancer Therapy ◽  
Nucleic Acids ◽  
Small Molecule ◽  
Tumor Suppressors ◽  
Cancer Biology ◽  
Genome Instability ◽  
Therapeutic Agents ◽  
Biological Processes ◽  
Dna And Rna ◽  
Small Molecule Ligands

Nucleic acids can adopt alternative secondary conformations including four-stranded structures known as quadruplexes. To date, quadruplexes have been demonstrated to exist both in human chromatin DNA and RNA. In particular, quadruplexes are found in guanine-rich sequences constituting G-quadruplexes, and in cytosine-rich sequences forming i-Motifs as a counterpart. Quadruplexes are associated with key biological processes ranging from transcription and translation of several oncogenes and tumor suppressors to telomeres maintenance and genome instability. In this context, quadruplexes have prompted investigations on their possible role in cancer biology and the evaluation of small-molecule ligands as potential therapeutic agents. This review aims to provide an updated close-up view of the literature on quadruplex ligands in cancer therapy, by grouping together ligands for DNA and RNA G-quadruplexes and DNA i-Motifs.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

Study of NSCLC cell migration promoted by NSCLC-Derived Extracellular Vesicle using atomic force microscopy

2021 ◽  
Author(s):  
Shuwei Wang ◽  
Jiajia Wang ◽  
Tuoyu Ju ◽  
Kaige Qu ◽  
Fan Yang ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Cell Migration ◽  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Cancer Microenvironment ◽  
Biological Processes ◽  
Force Microscopy ◽  
Atomic Force ◽  
Cellular Components

Extracellular Vesicles (EVs) secreted by cancer cells have a key role in the cancer microenvironment and progression. Previous studies have mainly focused on molecular functions, cellular components and biological processes...

scholarly journals The Multifaceted Roles of USP15 in Signal Transduction

2021 ◽  
Vol 22 (9) ◽  
pp. 4728
Author(s):  
Tanuza Das ◽  
Eun Joo Song ◽  
Eunice EunKyeong Kim
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Cellular Networks ◽  
Clinical Applications ◽  
Regulatory Mechanisms ◽  
Signaling Networks ◽  
Post Translational Modification ◽  
Comprehensive Overview ◽  
E3 Ligases ◽  
Disease Markers

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator.

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