scholarly journals The Role of Glycosylation in Melanoma Progression

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2136
Author(s):  
Chiara De Vellis ◽  
Silvia Pietrobono ◽  
Barbara Stecca
Keyword(s):  
Early Stage ◽  
Large Body ◽  
Surgical Excision ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Aberrant Glycosylation ◽  
Melanoma Progression ◽  
Glycosidic Bonds ◽  
Tumor Types

Malignant melanoma is the most aggressive form of skin cancer, which originates from the malignant transformation of melanocytes, the melanin-producing cells of the skin. Melanoma progression is typically described as a stepwise process in which metastasis formation ensues late during disease. A large body of evidence has shown that the accumulation of genetic and epigenetic alterations drives melanoma progression through the different steps. Mortality in melanoma is associated with metastatic disease. Accordingly, early-stage melanoma can be cured in the majority of cases by surgical excision, while late-stage melanoma is a highly lethal disease. Glycosylation is a post-translational modification that involves the transfer of glycosyl moieties to specific amino acid residues of proteins to form glycosidic bonds through the activity of glycosyltransferases. Aberrant glycosylation is considered a hallmark of cancer as it occurs in the majority of tumor types, including melanoma. The most widely occurring glycosylation changes in melanoma are represented by sialylation, fucosylation, and N- and I-glycan branching. In this review, we discuss the role of glycosylation in melanoma and provide insights on the mechanisms by which aberrant glycosylation promotes melanoma progression through activation of invasion and metastasis, immune evasion and cell proliferation.

scholarly journals Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

2020 ◽  
Vol 22 (1) ◽  
pp. 190
Author(s):  
Fulvio Borella ◽  
Mario Preti ◽  
Luca Bertero ◽  
Giammarco Collemi ◽  
Isabella Castellano ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
State Of The Art ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Survival Rates ◽  
Younger Women ◽  
Multiple Tumor ◽  
Tumor Types

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

SUMO: getting it on

2007 ◽  
Vol 35 (6) ◽  
pp. 1409-1413 ◽  
Author(s):  
J. Anckar ◽  
L. Sistonen
Keyword(s):  
Biological Processes ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Sumo Conjugation ◽  
Lysine Residues ◽  
Ubiquitin Conjugating Enzyme ◽  
Specificity Determinants ◽  
Conjugating Enzyme

Post-translational modification of cellular proteins by the SUMO (small ubiquitin-related modifier) is involved in numerous modes of regulation in widely different biological processes. In contrast with ubiquitination, SUMO conjugation is highly specific in terms of target lysine residues, but many aspects of substrate and lysine selection by the SUMO conjugating machinery are still poorly understood. SUMOylation events usually occur on the ΨKXE SUMO consensus motifs, which mediate binding to Ubc9 (ubiquitin-conjugating enzyme 9), the SUMO E2 conjugating enzyme. Although most, if not all, SUMO conjugations are catalysed by Ubc9, far from all ΨKXE tetrapeptides are modified, demonstrating a need for additional specificity determinants in SUMOylation. Recent results intimately link regulation of SUMOylation to other post-translational modifications, including phosphorylation and acetylation and reveal that certain lysine residues are marked for SUMOylation by negatively charged amino acid residues or phosphorylation events immediately downstream of the consensus site. In the present review, we explore the intriguing role of extended motifs in the regulation of SUMO conjugation.

Role of the Cyclin-Dependent Kinase Inhibitor CDKN2A in Familial Melanoma

1998 ◽  
Vol 2 (3) ◽  
pp. 172-179 ◽  
Author(s):  
David Hogg ◽  
Herbert Brill ◽  
Ling Liu ◽  
Jose Monzon ◽  
Anne Summers ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Kinase Inhibitor ◽  
Early Stage ◽  
Surgical Excision ◽  
Cyclin Dependent Kinase ◽  
Dominant Form ◽  
Familial Melanoma ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Autosomal Dominant Form

Background: Approximately 8 to 12% of melanoma appears to be inherited in an autosomal dominant form. Although most early stage melanomas can be treated successfully by simple surgical excision, patients with advanced disease are rarely cured even with aggressive chemotherapy and/or immunotherapy. Objective: There is now compelling evidence that germline mutations of the CDKN2A gene on chromosome 9p21 predispose to melanoma in a subset of melanoma-prone families. In this article the evidence for the role of CDKN2A in the genesis of familial melanoma is reviewed and the implications of genetic testing in families with this disease are discussed. Conclusion: The identification and subsequent surveillance of unaffected individuals who have a genetic predisposition to melanoma may lead to the detection of early (curable) melanomas and to a reduction in mortality.

scholarly journals Radiation-Induced Sarcoma following Treatment of Breast Cancer

1998 ◽  
Vol 5 (5) ◽  
pp. 425-432 ◽  
Author(s):  
Christiana M. Brenin ◽  
William Small ◽  
Mark S. Talamonti ◽  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Radiation Treatment ◽  
Early Stage ◽  
Surgical Excision ◽  
Breast Cancer Patients ◽  
Delay In Diagnosis ◽  
Delayed Treatment ◽  
Average Latency ◽  
Radiation Induced

Background Radiation therapy (XRT) is an important modality in the treatment of cancer, and XRT is now commonly utilized in the treatment of early-stage breast cancer. However, its use has occasionally resulted in the development of secondary malignancies. We present a critical review of radiation- induced sarcoma (RIS) that develops after irradiation for the treatment of breast cancer. Methods The case of a patient who developed sarcoma after radiation for breast cancer is presented, and current literature on RIS is reviewed. The role of XRT in the development of RIS is examined, and the evaluation and treatment of these malignancies are reviewed. Results RIS occurs in 0.2% of patients following treatment of breast cancer. The role of radiation in the development of RIS has been clearly demonstrated. Clinical presentation varies, and diagnosis is commonly delayed. Treatment consists of wide surgical excision. The role of chemotherapy is controversial. Conclusions The occurrence of RIS following treatment of breast cancer is rare. Its development has an average latency of over 10 years and likely correlates with the dose and technique of the radiation treatment. The prognosis of patients with RIS following treatment for breast cancer is poor predominantly due to a delay in diagnosis. However, the benefit derived by breast cancer patients from XRT far outweighs the risk of RIS and should not affect the decision to treat these patients with this modality.

scholarly journals The Role of Autophagy in Pancreatic Cancer—Recent Advances

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 7 ◽  
Author(s):  
Maria New ◽  
Sharon Tooze
Keyword(s):  
Pancreatic Cancer ◽  
Early Stage ◽  
Large Body ◽  
Ductal Adenocarcinoma ◽  
Improve Treatment ◽  
Recent Advances ◽  
Dismal Prognosis ◽  
Tumor Survival ◽  
Metastasis Development

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with a 5-year survival rate of only 9%, despite ongoing efforts to improve treatment. This dismal prognosis is due to the difficulty of early stage diagnosis, drug resistance, and likelihood of metastasis development. It is therefore of great importance to identify appropriate therapeutic targets and gain a greater understanding of PDAC biology. Autophagy is a membrane-mediated degradation and recycling mechanism, which is crucial for cell homeostasis. There is evidence for both a tumor-suppressive and a tumor-promoting role of autophagy in cancer, and this is likely context dependent. Within PDAC, a large body of evidence points towards autophagy being required for tumor survival and metabolism. In this review, we describe the recent advances in the understanding of the role and regulation of autophagy in PDAC.

scholarly journals Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Shih-Chang Chien ◽  
Yueh-Chen Wu ◽  
Zeng-Weng Chen ◽  
Wen-Chin Yang
Keyword(s):  
Therapeutic Potential ◽  
Autoimmune Diabetes ◽  
Early Stage ◽  
Large Body ◽  
Autoimmune Disorder ◽  
Biological Properties ◽  
Naturally Occurring ◽  
New Strategy ◽  
Made In

Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

scholarly journals The Role of Post-Translational Modifications of Chemokines by CD26 in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4247
Author(s):  
Alexandra De Zutter ◽  
Jo Van Damme ◽  
Sofie Struyf
Keyword(s):  
Large Family ◽  
Tumor Type ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Central Function ◽  
Post Translational Modifications ◽  
Specific Amino Acid ◽  
Cancer Setting ◽  
Penultimate Proline

Chemokines are a large family of small chemotactic cytokines that fulfill a central function in cancer. Both tumor-promoting and -impeding roles have been ascribed to chemokines, which they exert in a direct or indirect manner. An important post-translational modification that regulates chemokine activity is the NH2-terminal truncation by peptidases. CD26 is a dipeptidyl peptidase (DPPIV), which typically clips a NH2-terminal dipeptide from the chemokine. With a certain degree of selectivity in terms of chemokine substrate, CD26 only recognizes chemokines with a penultimate proline or alanine. Chemokines can be protected against CD26 recognition by specific amino acid residues within the chemokine structure, by oligomerization or by binding to cellular glycosaminoglycans (GAGs). Upon truncation, the binding affinity for receptors and GAGs is altered, which influences chemokine function. The consequences of CD26-mediated clipping vary, as unchanged, enhanced, and reduced activities are reported. In tumors, CD26 most likely has the most profound effect on CXCL12 and the interferon (IFN)-inducible CXCR3 ligands, which are converted into receptor antagonists upon truncation. Depending on the tumor type, expression of CD26 is upregulated or downregulated and often results in the preferential generation of the chemokine isoform most favorable for tumor progression. Considering the tight relationship between chemokine sequence and chemokine binding specificity, molecules with the appropriate characteristics can be chemically engineered to provide innovative therapeutic strategies in a cancer setting.

scholarly journals The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Alyssa L. Becker ◽  
Evan L. Carpenter ◽  
Andrzej T. Slominski ◽  
Arup K. Indra
Keyword(s):  
Vitamin D ◽  
Prognostic Marker ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Treatment Resistance ◽  
Surgical Excision ◽  
1,25 Dihydroxy Vitamin D3

Melanoma is the malignant transformation of melanocytes and represents the most lethal form of skin cancer. While early-stage melanoma localized to the skin can be cured with surgical excision, metastatic melanoma often requires a multi-pronged approach and even then can exhibit treatment resistance. Understanding the molecular mechanisms involved in the pathogenesis of melanoma could lead to novel diagnostic, prognostic, and therapeutic strategies to ultimately decrease morbidity and mortality. One emerging candidate that may have value as both a prognostic marker and in a therapeutic context is the vitamin D receptor (VDR). VDR is a nuclear steroid hormone receptor activated by 1,25 dihydroxy-vitamin D3 [calcitriol, 1,25(OH)2D3]. While 1,25 dihydroxy-vitamin D3 is typically thought of in relation to calcium metabolism, it also plays an important role in cell proliferation, differentiation, programmed-cell death as well as photoprotection. This review discusses the role of VDR in the crosstalk between keratinocytes and melanocytes during melanomagenesis and summarizes the clinical data regarding VDR polymorphisms, VDR as a prognostic marker, and potential uses of vitamin D and its analogs as an adjuvant treatment for melanoma.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

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