scholarly journals FUT8 Alpha-(1,6)-Fucosyltransferase in Cancer

2021 ◽  
Vol 22 (1) ◽  
pp. 455
Author(s):  
Kayla Bastian ◽  
Emma Scott ◽  
David J. Elliott ◽  
Jennifer Munkley
Keyword(s):  
Immune Evasion ◽  
Tumour Progression ◽  
Critical Role ◽  
Critical Factor ◽  
Cancer Therapeutics ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Α3β1 Integrin ◽  
Universal Feature ◽  
Core Fucosylation

Aberrant glycosylation is a universal feature of cancer cells that can impact all steps in tumour progression from malignant transformation to metastasis and immune evasion. One key change in tumour glycosylation is altered core fucosylation. Core fucosylation is driven by fucosyltransferase 8 (FUT8), which catalyses the addition of α1,6-fucose to the innermost GlcNAc residue of N-glycans. FUT8 is frequently upregulated in cancer, and plays a critical role in immune evasion, antibody-dependent cellular cytotoxicity (ADCC), and the regulation of TGF-β, EGF, α3β1 integrin and E-Cadherin. Here, we summarise the role of FUT8 in various cancers (including lung, liver, colorectal, ovarian, prostate, breast, melanoma, thyroid, and pancreatic), discuss the potential mechanisms involved, and outline opportunities to exploit FUT8 as a critical factor in cancer therapeutics in the future.

scholarly journals The Duality of Caspases in Cancer, as Told through the Fly

2021 ◽  
Vol 22 (16) ◽  
pp. 8927
Author(s):  
Caitlin Hounsell ◽  
Yun Fan
Keyword(s):  
Tumour Progression ◽  
Critical Role ◽  
Dual Role ◽  
Activity Level ◽  
Therapeutic Approaches ◽  
Cancer Treatments ◽  
Aspartic Proteases ◽  
Critical Components ◽  
Established Role

Caspases, a family of cysteine-aspartic proteases, have an established role as critical components in the activation and initiation of apoptosis. Alongside this a variety of non-apoptotic caspase functions in proliferation, differentiation, cellular plasticity and cell migration have been reported. The activity level and context are important factors in determining caspase function. As a consequence of their critical role in apoptosis and beyond, caspases are uniquely situated to have pathological roles, including in cancer. Altered caspase function is a common trait in a variety of cancers, with apoptotic evasion defined as a “hallmark of cancer”. However, the role that caspases play in cancer is much more complex, acting both to prevent and to promote tumourigenesis. This review focuses on the major findings in Drosophila on the dual role of caspases in tumourigenesis. This has major implications for cancer treatments, including chemotherapy and radiotherapy, with the activation of apoptosis being the end goal. However, such treatments may inadvertently have adverse effects on promoting tumour progression and acerbating the cancer. A comprehensive understanding of the dual role of caspases will aid in the development of successful cancer therapeutic approaches.

scholarly journals PSYCHOGEOGRAPHICAL EXPERIENCE BETWEEN THE SELF AND THE PLACE

2022 ◽  
Vol 7 (1) ◽  
pp. 243-263
Author(s):  
Mohd Fadhli Shah Khaidzir ◽  
Ruzy Suliza Hashim ◽  
Noraini Md. Yusof
Keyword(s):  
Critical Role ◽  
Critical Factor ◽  
The Self ◽  
Future Research ◽  
Future Studies ◽  
Place Meaning ◽  
Solid Foundation ◽  
Self Discovery ◽  
Attachment Place

Background and Purpose: The absence of psychogeographical awareness is a critical factor contributing to the lackadaisical attitudes towards the place and its environment. As a result, it enables an individual to fully experience a location, both physically and intellectually, while also gaining a feeling of self-discovery and self-realisation.   Methodology: The purpose of this study was to examine the responses of a group of individuals who participated in a field observation. 40 participants from a Malaysian university's foundation level were brought to Malacca to experience the environment's geographical scenery at their own leisure. The survey data was then manually transcribed and analysed in accordance with the study's aim.   Findings: Interactions with individuals and observation of features in the countryside and urban surroundings enabled participants to go on a psychogeographical journey that influenced their way of thinking and behaving. All participants felt that the journey had influenced their experiences and perspectives on their thinking and behaviour, highlighting the critical role of this notion in establishing the connection between place and self.   Contributions:  The findings of this study provide a solid foundation for future research in the field of psychogeography. The data may be used as a baseline for future studies to determine whether a comparable impact exists in other locations, with or without significant features like those found in Malacca.   Keywords: Psychogeography, place attachment, place meaning, self-discovery, Malacca.   Cite as: Khaidzir, M. F. S., Hashim, R. S., & Md. Yusof, N. (2022). Psychogeographical experience between the self and the place.  Journal of Nusantara Studies, 7(1), 243-263. http://dx.doi.org/10.24200/jonus.vol7iss1pp243-263

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
pp. 1-23
Author(s):  
Divya Adiga ◽  
Raghu Radhakrishnan ◽  
Sanjiban Chakrabarty ◽  
Prashant Kumar ◽  
Shama Prasada Kabekkodu
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Microenvironmental Factors ◽  
Favorable Clinical Outcome

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca<sup>2+</sup>) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca<sup>2+</sup> signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca<sup>2+</sup> signal remodeling in the regulation of EMT and metastasis in cancer.

scholarly journals Insights into the mysterious genetic variation profile oftprKinTreponema pallidumunder the development of natural human syphilis infection

2019 ◽  
Author(s):  
Dan Liu ◽  
Man-Li Tong ◽  
Yong Lin ◽  
Li-Li Liu ◽  
Li-Rong Lin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Immune Evasion ◽  
High Frequency ◽  
Critical Role ◽  
Treponema Pallidum ◽  
Secondary Syphilis ◽  
Human Infection ◽  
Amino Acid Sequences ◽  
Potential Vaccine

AbstractAlthough the variations of thetprKgene inTreponema pallidumwere considered to play a critical role in the pathogenesis of syphilis, how actual variable characteristics oftprKin the course of natural human infection enabling the pathogen’s survive has thus far remained unclear. Here, we performed NGS to investigatetprKofT. pallidumdirectly from primary and secondary syphilis samples. Compared with diversity intprKof the strains from primary syphilis samples, there were more mixture variants found within seven V regions of thetprKgene among the strains from secondary syphilis samples, and the frequencies of predominant sequences within V regions oftprKwere generally decreased (less than 80%) with the proportion of minor variants in 10-60% increasing. Noteworthy, the variations within V regions oftprKalways obeyed a strict 3 bp changing pattern. AndtprKin the strains from the two-stage samples kept some stable amino acid sequences within V regions. Particularly, the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1 not only presented a high proportion of inter-population sharing, but also presented a relatively high frequency (above 80%) in the populations. Besides,tprKalways demonstrated remarkable variability in V6 at both the intra- and inter-strain levels regardless of the course. These findings unveiled that the different profile oftprK in T. pallidumdirectly from primary and secondary syphilis samples, indicating that throughout the development of syphilisT. pallidumconstantly varies its domaintprKgene to obtain the best adaptation to the host. While this changing was always subjected a strict gene conversion mechanism to keep an abnormal TprK. The highly stable peptides found in V1 would probably be promising potential vaccine components. And the highly heterogenetic regions (e.g. V6) could provide insight into the mysterious role oftprKin immune evasion.Author summaryAlthough the variations of thetprKgene inTreponema pallidumwere considered to play a critical role in the pathogenesis of syphilis, how actual variable characteristics oftprKin the course of natural human infection enabling the pathogen’s survive has thus far remained unclear. Here, we performed next-generation sequencing, a more sensitive and reliable approach, to investigatetprKofTreponema pallidumdirectly from primary and secondary syphilis patients, revealing that the profile oftprKinT. pallidumfrom the two-stage samples was different. Within the strains from secondary syphilis patients, more mixture variants within seven V regions oftprKwere found, the frequencies of their predominant sequences were generally decreased with the proportion of minor variants in 10-60% was increased. And the variations within V regions oftprKalways obeyed a strict 3 bp changing pattern. Noteworthy, the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1 presented a high proportion of inter-population sharing and presented a relatively high frequency in the populations. And V6 region always demonstrated remarkable variability at intra- and inter-patient levels regardless of the course. These findings provide insights into the mysterious role of TprK in immune evasion and for further exploring the potential vaccine components.

scholarly journals Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Fei Zhang ◽  
Xu Pei ◽  
Ke-Sang Li ◽  
Li-Na Jin ◽  
Fei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Immune Evasion ◽  
Critical Role ◽  
Circular Rna ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Background Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment. Methods The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p. Results Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy. Conclusion Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.

Critical role of transcription factor PU.1 in the expression of CD80 and CD86 on dendritic cells

Blood ◽  
2011 ◽  
Vol 117 (7) ◽  
pp. 2211-2222 ◽  
Author(s):  
Shunsuke Kanada ◽  
Chiharu Nishiyama ◽  
Nobuhiro Nakano ◽  
Ryuyo Suzuki ◽  
Keiko Maeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Transcription Factor ◽  
Critical Role ◽  
Critical Factor ◽  
Contact Hypersensitivity ◽  
Murine Bone Marrow ◽  
Gel Shift Assay ◽  
Interfering Rna

Abstract In this study, we investigated the role of a transcription factor, PU.1, in the regulation of CD80 and CD86 expression in dendritic cells (DCs). A chromatin immunoprecipitation assay revealed that PU.1 is constitutively bound to the CD80 and CD86 promoters in bone marrow–derived DCs. In addition, co-expression of PU.1 resulted in the transactivation of the CD80 and CD86 promoters in a reporter assay. The binding of PU.1 to cis-enhancing regions was confirmed by electromobility gel-shift assay. As expected, inhibition of PU.1 expression by short interfering RNA (siRNA) in bone marrow–derived DCs resulted in marked down-regulation of CD80 and CD86 expression. Moreover, overexpression of PU.1 in murine bone marrow–derived lineage-negative cells induced the expression of CD80 and CD86 in the absence of monocyte/DC-related growth factors and/or cytokines. Based on these results, we conclude that PU.1 is a critical factor for the expression of CD80 and CD86. We also found that subcutaneous injection of PU.1 siRNA or topical application of a cream-emulsified PU.1 siRNA efficiently inhibited murine contact hypersensitivity. Our results suggest that PU.1 is a potential target for the treatment of immune-related diseases.

scholarly journals E3 ubiquitin ligase HECTD2 mediates melanoma progression and immune evasion

Oncogene ◽  
2021 ◽  
Author(s):  
Eleonora Ottina ◽  
Veera Panova ◽  
Laura Doglio ◽  
Anastasiya Kazachenka ◽  
Georgina Cornish ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cell ◽  
Ubiquitin Ligase ◽  
Immune Evasion ◽  
Tumour Progression ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Proteasome System ◽  
Tumour Immunity ◽  
Murine Melanoma

AbstractThe ubiquitin-proteasome system maintains protein homoeostasis, underpins the cell cycle, and is dysregulated in cancer. However, the role of individual E3 ubiquitin ligases, which mediate the final step in ubiquitin-mediated proteolysis, remains incompletely understood. Identified through screening for cancer-specific endogenous retroviral transcripts, we show that the little-studied E3 ubiquitin ligase HECTD2 exerts dominant control of tumour progression in melanoma. HECTD2 cell autonomously drives the proliferation of human and murine melanoma cells by accelerating the cell cycle. HECTD2 additionally regulates cancer cell production of immune mediators, initiating multiple immune suppressive pathways, which include the cyclooxygenase 2 (COX2) pathway. Accordingly, higher HECTD2 expression is associated with weaker anti-tumour immunity and unfavourable outcome of PD-1 blockade in human melanoma and counteracts immunity against a model tumour antigen in murine melanoma. This central, multifaceted role of HECTD2 in cancer cell-autonomous proliferation and in immune evasion may provide a single target for a multipronged therapy of melanoma.

scholarly journals Targeting Aberrant Sialylation to Treat Cancer

Medicines ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 102 ◽  
Author(s):  
Jennifer Munkley ◽  
Emma Scott
Keyword(s):  
Clinical Trials ◽  
Sialic Acid ◽  
Immune Evasion ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Cancer Therapeutics ◽  
Metastatic Cascade ◽  
Cancer Hallmarks ◽  
Therapeutic Value ◽  
Surface Carbohydrates

Cell surface carbohydrates (known as glycans) are often aberrantly expressed or found at atypical levels in cancer. Glycans can impact all steps in tumour progression, from malignant transformation to metastasis, and have roles in all the cancer hallmarks. An increased understanding of glycans in the metastatic cascade offers exciting new therapeutic opportunities. Glycan-based targeting strategies are currently being tested in clinical trials and are a rich and untapped frontier for development. As we learn more about cancer glycobiology, new targets will continue to emerge for drug design. One key change in tumour glycosylation is the upregulation of cancer-associated sialylated glycans. Abnormal sialylation is integral to tumour growth, metastasis and immune evasion; therefore, targeting sialic acid moieties in cancer could be of high therapeutic value. Here, we summarise the changes to sialic acid biology in cancer and discuss recent advances and technologies bringing sialic-acid targeting treatments to the forefront of cancer therapeutics.

scholarly journals Low neoantigen expression and poor T cell priming underlie early immune escape in cancer

2020 ◽  
Author(s):  
Peter Westcott ◽  
Nathan Sacks ◽  
Jason Schenkel ◽  
Olivia Smith ◽  
Daniel Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Evasion ◽  
Immune Escape ◽  
Critical Role ◽  
Immune Surveillance ◽  
Tumor Rejection ◽  
Variable Expression ◽  
High Affinity ◽  
T Cell Priming

Abstract Immune evasion is a hallmark of cancer, and therapies that restore immune surveillance have proven highly effective in cancers with high tumor mutation burden (TMB) (e.g. microsatellite instable (MSI) colorectal cancer (CRC)). Whether low TMB cancers, which are largely refractory to immunotherapy, harbor T cell neoantigens capable of engaging adaptive immunity remains unclear. Here, we show that the majority of microsatellite stable (MSS) CRC harbors predicted high-affinity neoantigens despite low TMB. Unexpectedly, these neoantigens are broadly expressed at lower levels relative to those in MSI CRC, suggesting a potential role of antigen expression in tumor immune surveillance. To test this, we developed a versatile platform for functional interrogation of neoantigens with variable expression and applied it to novel preclinical colonoscopy-guided mouse models of CRC. While high expression of multiple high-affinity MHC-I-restricted neoantigens universally resulted in tumor rejection, low expression resulted in poor T cell priming and tumor progression. Strikingly, experimental or therapeutic rescue of priming rendered T cells fully capable of controlling tumors with low neoantigen expression. These findings underscore a critical role of neoantigen expression levels in immune evasion and suggest that poor expression or presentation may be a general feature of neoantigens acquired early in tumorigenesis. Finally, poorly expressed neoantigens, commonly excluded in tumor vaccine pipelines, may hold untapped therapeutic potential.

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