FAT10: Function and Relationship with Cancer

Posttranslational protein modifications are known to be extensively involved in cancer, and a growing number of studies have revealed that the ubiquitin-like modifier FAT10 is directly involved in cancer development. FAT10 was found to be highly upregulated in various cancer types, such as glioma, hepatocellular carcinoma, breast cancer and gastrointestinal cancer. Protein FAT10ylation and interactions with FAT10 lead to the functional change of proteins, including proteasomal degradation, subcellular delocalization and stabilization, eventually having significant effects on cancer cell proliferation, invasion, metastasis and even tumorigenesis. In this review, we summarized the current knowledge on FAT10 and discussed its biological functions in cancer, as well as potential therapeutic strategies based on the FAT10 pathway.

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Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽

10.3390/cells9010114 ◽

2020 ◽

Vol 9 (1) ◽

pp. 114

Author(s):

Lisa Linck-Paulus ◽

Claus Hellerbrand ◽

Anja K. Bosserhoff ◽

Peter Dietrich

Keyword(s):

Cancer Progression ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Therapeutic Targets ◽

Genetic Alterations ◽

Therapeutic Strategies ◽

The Future ◽

Associated Proteins ◽

Cancer Types ◽

Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

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The oxytocin receptor signalling system and breast cancer: a critical review

Oncogene ◽

10.1038/s41388-020-01415-8 ◽

2020 ◽

Vol 39 (37) ◽

pp. 5917-5932 ◽

Cited By ~ 1

Author(s):

Huiping Liu ◽

Christian W. Gruber ◽

Paul F. Alewood ◽

Andreas Möller ◽

Markus Muttenthaler

Keyword(s):

Breast Cancer ◽

Current Knowledge ◽

Oxytocin Receptor ◽

Cancer Development ◽

Breast Cancer Cell Lines ◽

Maternal Behaviour ◽

Supporting Evidence ◽

Breast Cancer Development ◽

Signalling System ◽

Cancer Management

Abstract Breast cancer is making up one-quarter of all new female cancer cases diagnosed worldwide. Breast cancer surgeries, radiation therapies, cytotoxic chemotherapies and targeted therapies have made significant progress and play a dominant role in breast cancer patient management. However, many challenges remain, including resistance to systemic therapies, tumour recurrence and metastasis. The cyclic neuropeptide oxytocin (OT) elicits a plethora of biological responses via the oxytocin receptor (OTR) in both the central and peripheral nervous system, including social bonding, stress, maternal behaviour, sexual activity, uterus contraction, milk ejection and cancer. As a typical member of the G protein-coupled receptor family, OTR represents also an intriguing target for cancer therapy. There is emerging evidence that OTR plays a role in breast cancer development and progression, and several breast cancer cell lines express OTR. However, despite supporting evidence that OT lowers breast cancer risks, its mechanistic role in breast cancer development and the related signalling pathways are not fully understood. Here, we review the current knowledge of the OT/OTR signalling system in healthy breast tissue as well as in breast cancer, and discuss OTR as a potential therapeutic target for breast cancer management.

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Integrative Pan-Cancer Analysis Reveals Decreased Melatonergic Gene Expression in Carcinogenesis and RORA as a Prognostic Marker for Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.643983 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yi Zou ◽

Huaqin Sun ◽

Yating Guo ◽

Yidan Shi ◽

Zhiyu Jiang ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Prognostic Marker ◽

Nuclear Receptor ◽

Expression Patterns ◽

Cancer Development ◽

Metabolic Genes ◽

Intracellular Receptor ◽

Cancer Types ◽

The Relationship

BackgroundMelatonin has been shown to play a protective role in the development and progression of cancer. However, the relationship between alterations in the melatonergic microenvironment and cancer development has remained unclear.MethodsWe performed a comprehensive investigation on 12 melatonergic genes and their relevance to cancer occurrence, progression and survival by integrating multi-omics data from microarray analysis and RNA sequencing across 11 cancer types. Specifically, the 12 melatonergic genes that we investigated, which reflect the melatonergic microenvironment, included three membrane receptor genes, three nuclear receptor genes, two intracellular receptor genes, one synthetic gene, and three metabolic genes.ResultsWidely coherent underexpression of nuclear receptor genes, intracellular receptor genes, and metabolic genes was observed in cancerous samples from multiple cancer types compared to that in normal samples. Furthermore, genomic and/or epigenetic alterations partially contributed to these abnormal expression patterns in cancerous samples. Moreover, the majority of melatonergic genes had significant prognostic effects in predicting overall survival. Nevertheless, few corresponding alterations in expression were observed during cancer progression, and alterations in expression patterns varied greatly across cancer types. However, the association of melatonergic genes with one specific cancer type, hepatocellular carcinoma, identified RORA as a tumor suppressor and a prognostic marker for patients with hepatocellular carcinoma.ConclusionsOverall, our study revealed decreased melatonergic gene expression in various cancers, which may help to better elucidate the relationship between melatonin and cancer development. Taken together, our findings highlight the potential prognostic significance of melatonergic genes in various cancers.

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Integrative Analysis the characterization of peroxiredoxins in pan-cancer

10.1101/2020.10.09.334086 ◽

2020 ◽

Author(s):

Lei Gao ◽

Jialin Meng ◽

Chuang Yue ◽

Xingyu Wu ◽

Quanxin Su ◽

...

Keyword(s):

Expression Profiles ◽

Genetic Alterations ◽

Comprehensive Analysis ◽

Biological Pathways ◽

Cancer Cell Proliferation ◽

Biological Functions ◽

Systematic Analysis ◽

Cancer Types ◽

Pan Cancer

AbstractPeroxiredoxins (PRDXs) are antioxidant enzymes protein family members that involves the process of several biological functions, such as differentiation, cell growth. Considerable evidence demonstrates that PRDXs play critical roles in the occurrence and development of carcinomas. However, a systematic analysis of PRDXs in cancers is deficiency. Therefore, we perform a comprehensive analysis of PRDXs in 33 cancer types including mRNA expression profiles, genetic alterations, methylation, prognostic values, potential biological pathways and target drugs. Moreover, we validated that PRDX6 could regulate cancer cell proliferation via JAK2-STAT3 pathway and involve into the process of cell cycle in bladder cancer.

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Signal Transduction of a Novel WBP2 Oncogene

Proceedings of the Singapore National Academy of Science ◽

10.1142/s2591722620400013 ◽

2020 ◽

Vol 14 (01) ◽

pp. 3-13

Author(s):

Tinghine Chu ◽

Sock Hong Seah ◽

Yoon Pin Lim

Keyword(s):

Breast Cancer ◽

Cancer Development ◽

Signalling Pathways ◽

Ww Domain ◽

Growing Body ◽

Cancer Types ◽

Near Future ◽

Oncogenic Signalling ◽

Hippo Signalling

WW-domain binding protein 2 (WBP2) was first discovered as a ligand of the WW-domain of Yes-associated Protein (YAP). A decade after its discovery, our laboratory implicated WBP2 in breast cancer development. Since then, WBP2 had also been shown to be involved in other types of cancer, such as glioma, liver and skin cancer. The oncogenic properties of WBP2 are mediated by several oncogenic signalling pathways, including EGFR, PI3K/Akt, ER, Wnt, and Hippo signalling pathways. Recently, WBP2 was demonstrated to play roles in diseases other than cancer, such as infertility and deafness. In the near future, we envisage a growing body of literature surrounding the role of WBP2 in more cancer types and signalling pathways.

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The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies

International Journal of Molecular Sciences ◽

10.3390/ijms21218102 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8102 ◽

Cited By ~ 1

Author(s):

Giovanni Zarrilli ◽

Gianluca Businello ◽

Maria Vittoria Dieci ◽

Silvia Paccagnella ◽

Valentina Carraro ◽

...

Keyword(s):

Breast Cancer ◽

Extracellular Matrix ◽

Tumor Microenvironment ◽

Metastatic Breast ◽

Therapeutic Strategies ◽

Cancer Development ◽

Lymphatic Endothelial Cells ◽

Metastatic Sites ◽

Novel Therapeutic Strategies ◽

Novel Therapeutic

Breast cancer evolves thanks to a dense and close interaction with the surrounding tumor microenvironment (TME). Fibroblasts, leukocytes, blood and lymphatic endothelial cells and extracellular matrix are the constituents of this entity, and they synergistically play a pivotal role in all of the stages of breast cancer development, from its onset to its metastatic spread. Moreover, it has been widely demonstrated that variations to the TME can correspond to prognosis variations. Breast cancer not only modulates the transformation of the environment within the mammary gland, but the same process is observed in metastases as well. In this minireview, we describe the features of TME within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.

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Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma

Journal of Hematology & Oncology ◽

10.1186/s13045-019-0782-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 16

Author(s):

Zeli Yin ◽

Chengyong Dong ◽

Keqiu Jiang ◽

Zhe Xu ◽

Rui Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Stromal Cell ◽

Causes Of Death ◽

Therapeutic Strategies ◽

Research Topic ◽

Cancer Associated Fibroblasts ◽

Biological Functions ◽

Cell Type ◽

Cellular Origin ◽

Heterogeneous Tissue

Abstract Hepatocellular carcinoma (HCC) is a lethal disease, and recurrence and metastasis are the major causes of death in HCC patients. Cancer-associated fibroblasts (CAFs), a major stromal cell type in the HCC microenvironment, promote HCC progression, and have gradually become a hot research topic in HCC-targeted therapy. This review comprehensively describes and discusses the heterogeneous tissue distribution, cellular origin, phenotype, and biological functions of HCC-associated fibroblasts. Furthermore, the possible use of CAFs for predicting HCC prognosis and in targeted therapeutic strategies is discussed, highlighting the critical roles of CAFs in HCC progression, diagnosis, and therapy.

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The Importance of Autophagy Regulation in Breast Cancer Development and Treatment

BioMed Research International ◽

10.1155/2014/710345 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 41

Author(s):

Joanna Magdalena Zarzynska

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Malignant Tumor ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Cell Stress ◽

Cancer Development ◽

Cancer Initiation ◽

Life Threatening

Breast cancer (BC) is a potentially life-threatening malignant tumor that still causes high mortality among women. One of the mechanisms through which cancer development could be controlled is autophagy. This process exerts different effects during the stages of cancer initiation and progression due to the occurring superimposition of signaling pathways of autophagy and carcinogenesis. Chronic inhibition of autophagy or autophagy deficiency promotes cancer, due to instability of the genome and defective cell growth and as a result of cell stress. However, increased induction of autophagy can become a mechanism which allows tumor cells to survive the conditions of hypoxia, acidosis, or chemotherapy. Therefore, in the development of cancer, autophagy is regarded as a double-edged sword. Determination of the molecular mechanisms underlying autophagy regulation and its role in tumorigenesis is an essential component of modern anticancer strategies. Results of scientific studies show that inhibition of autophagy may enhance the effectiveness of currently used anticancer drugs and other therapies (like radiotherapy). However, in some cases, the promotion of autophagy can induce death and, hence, elimination of the cancer cells and reduction of tumor size. This review summarizes the current knowledge on autophagy regulation in BC and up-to-date anticancer strategies correlated with autophagy.

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The Functions and Unique Features of LncRNAs in Cancer Development and Tumorigenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22020632 ◽

2021 ◽

Vol 22 (2) ◽

pp. 632

Author(s):

Kenzui Taniue ◽

Nobuyoshi Akimitsu

Keyword(s):

Cancer Biology ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Cancer Development ◽

Biological Functions ◽

Protein Coding ◽

Rna Molecules ◽

The Past ◽

Cancer Phenotypes ◽

Coding Potential

Over the past decades, research on cancer biology has focused on the involvement of protein-coding genes in cancer development. Long noncoding RNAs (lncRNAs), which are transcripts longer than 200 nucleotides that lack protein-coding potential, are an important class of RNA molecules that are involved in a variety of biological functions. Although the functions of a majority of lncRNAs have yet to be clarified, some lncRNAs have been shown to be associated with human diseases such as cancer. LncRNAs have been shown to contribute to many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, protein and RNA. Here we describe the literature regarding the biogenesis and features of lncRNAs. We also present an overview of the current knowledge regarding the roles of lncRNAs in cancer from the view of various aspects of cellular homeostasis, including proliferation, survival, migration and genomic stability. Furthermore, we discuss the methodologies used to identify the function of lncRNAs in cancer development and tumorigenesis. Better understanding of the molecular mechanisms involving lncRNA functions in cancer is critical for the development of diagnostic and therapeutic strategies against tumorigenesis.

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The Involvement of Arginase and Nitric Oxide Synthase in Breast Cancer Development: Arginase and NO Synthase as Therapeutic Targets in Cancer

BioMed Research International ◽

10.1155/2018/8696923 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 12

Author(s):

Nikolay Avtandilyan ◽

Hayarpi Javrushyan ◽

Gayane Petrosyan ◽

Armen Trchounian

Keyword(s):

Breast Cancer ◽

Nitric Oxide ◽

Human Serum ◽

No Synthase ◽

Cancer Development ◽

Cancer Cell Proliferation ◽

Antitumor Effects ◽

Before And After ◽

Oxide Synthase ◽

Burk Plot

It is well established that, during development of malignancies, metabolic changes occur, including alterations of enzyme activities and isoenzyme expression. Arginase and nitric oxide (NO) synthase (NOS) are two of those enzymes considered to be involved in tumorigenesis. The goal of this article was to study the involvement of arginase and NOS in the development of different stages of breast cancer. Our results have shown that human serum arginase activity and NO (resp., and NOS activity) and polyamines quantities increased in parallel with cancer stage progression and decreased after neoadjuvant chemotherapy. For breast cancer, the only isoenzyme of arginase expressed in serum before and after chemotherapy was in a cationic form. The data of Lineweaver-Burk plot with aKmvalue of 2 mM was calculated, which is characteristic for human liver type isoform of arginase. During electrophoresis at pH 8.9, the enzyme exhibited high electrophoretic mobility and was detected near the anode. The presented results demonstrated that arginase in human serum with breast cancer and after chemotherapy is not polymorphic. We suggest that arginase and NOS inhibition has antitumor effects on cancer development, as it can inhibit polyamines and NO levels, a precursor of cancer cell proliferation, metastasis, and tumor angiogenesis.

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