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Article ; Online: Cellular zinc metabolism and zinc signaling

Bonan Chen / Peiyao Yu / Wai Nok Chan / Fuda Xie / Yigan Zhang / Li Liang / Kam Tong Leung / Kwok Wai Lo / Jun Yu / Gary M. K. Tse / Wei Kang / Ka Fai To

Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-

from biological functions to diseases and therapeutic targets

2024 Volume 41

Abstract: Abstract Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular ... ...

Abstract	Abstract Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc’s cellular metabolism, particularly the functions of zinc transporters and storage mechanisms during cancer progression. Zinc transportation is under the control of two major transporter families: SLC30 (ZnT) for the excretion of zinc and SLC39 (ZIP) for the zinc intake. Additionally, the storage of this essential element is predominantly mediated by metallothioneins (MTs). This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression, with a special focus on cancer. We also compile a summary of clinical trials involving zinc ions. Given the main localization of zinc transporters at the cell membrane, the potential for targeted therapies, including small molecules and monoclonal antibodies, offers promising avenues for future exploration.
Keywords	Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Omics-wide quantitative B-cell infiltration analyses identify GPR18 for human cancer prognosis with superiority over CD20

Yuchen Liu / Li Wang / Kwok-Wai Lo / Vivian Wai Yan Lui

Communications Biology, Vol 3, Iss 1, Pp 1-

2020 Volume 11

Abstract: Yuchen Liu et al. show that GPR18 serves as a superior prognostic marker across nine cancers over CD20 by TIL-B omics analyses. GPR18 expressions in tumors are strongly correlated with major T-cell functionality scores, suggesting its functional link to ... ...

Abstract	Yuchen Liu et al. show that GPR18 serves as a superior prognostic marker across nine cancers over CD20 by TIL-B omics analyses. GPR18 expressions in tumors are strongly correlated with major T-cell functionality scores, suggesting its functional link to cytolytic T-cell activity in cancer.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Single Agent and Synergistic Activity of Maritoclax with ABT-263 in Nasopharyngeal Carcinoma (NPC) Cell Lines.

Xiang, Benedict Lian Shi / Kwok-Wai, Lo / Soo-Beng, Alan Khoo / Mohana-Kumaran, Nethia

Tropical life sciences research

2020 Volume 31, Issue 3, Page(s) 1–13

Abstract: The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported ... ...

Abstract	The BCL-2 anti-apoptotic proteins are over-expressed in many cancers and hence are attractive therapeutic targets. In this study, we tested the sensitivity of two Nasopharyngeal Carcinoma (NPC) cell lines HK1 and C666-1 to Maritoclax, which is reported to repress anti-apoptotic protein MCL-1 and BH3 mimetic ABT-263, which selectively inhibits anti-apoptotic proteins BCL-2, BCL-XL and BCL-w. We investigated the sensitisation of the NPC cell lines to these drugs using the SYBR Green I assay and 3D NPC spheroids. We report that Maritoclax repressed anti-apoptotic proteins MCL-1, BCL-2, and BCL-XL in a dose- and time-dependent manner and displayed a single agent activity in inhibiting cell proliferation of the NPC cell lines. Moreover, combination of Maritoclax and ABT-263 exhibited synergistic antiproliferative effect in the HK1 cells. Similar results were obtained in the 3D spheroids generated from the HK1 cells. More notably, 3D HK1 spheroids either treated with single agent Maritoclax or combination with ABT-263, over 10 days, did not develop resistance to the treatment rapidly. Collectively, the findings illustrate that Maritoclax as a single agent or combination with BH3 mimetics could be potentially useful as treatment strategies for the management of NPC.
Language	English
Publishing date	2020-10-15
Publishing country	Malaysia
Document type	Journal Article
ZDB-ID	2607038-8
ISSN	2180-4249 ; 1985-3718
ISSN (online)	2180-4249
ISSN	1985-3718
DOI	10.21315/tlsr2020.31.3.1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cancer stem-like cells in Epstein-Barr virus-associated nasopharyngeal carcinoma

Samantha Wei-Man Lun / Siu-Tim Cheung / Kwok-Wai Lo

Chinese Journal of Cancer, Vol 33, Iss 11, Pp 529-

2014 Volume 538

Abstract: Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal ... ...

Abstract	Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells (CSCs) have the ability to self-renew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBV-associated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A)], cellular microRNAs, and adenosine triphosphate (ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.
Keywords	Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	571
Language	English
Publishing date	2014-11-01T00:00:00Z
Publisher	Cancer Center,Sun Yat-sen University
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of miR-96/EVI1/miR-449a Axis in the Nasopharyngeal Carcinoma Cell Migration and Tumor Sphere Formation

Lai-Sheung Chan / Hong-Lok Lung / Roger Kai-Cheong Ngan / Anne Wing-Mui Lee / Sai Wah Tsao / Kwok-Wai Lo / Michael Kahn / Maria Li Lung / Rotraud Wieser / Nai-Ki Mak

International Journal of Molecular Sciences, Vol 21, Iss 5495, p

2020 Volume 5495

Abstract: The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling ... ...

Abstract	The Wnt signaling pathway is one of the major signaling pathways used by cancer stem cells (CSC). Ecotropic Viral Integration Site 1 (EVI1) has recently been shown to regulate oncogenic development of tumor cells by interacting with multiple signaling pathways, including the Wnt signaling. In the present study, we found that the Wnt modulator ICG-001 could inhibit the expression of EVI1 in nasopharyngeal carcinoma (NPC) cells. Results from loss-of-function and gain-of-function studies revealed that EVI1 expression positively regulated both NPC cell migration and growth of CSC-enriched tumor spheres. Subsequent studies indicated ICG-001 inhibited EVI1 expression via upregulated expression of miR-96. Results from EVI1 3′UTR luciferase reporter assay confirmed that EVI1 is a direct target of miR-96. Further mechanistic studies revealed that ICG-001, overexpression of miR-96, or knockdown of EVI1 expression could restore the expression of miR-449a. The suppressive effect of miR-449a on the cell migration and tumor sphere formation was confirmed in NPC cells. Taken together, the miR-96/EVI1/miR-449a axis is a novel pathway involved in ICG-001-mediated inhibition of NPC cell migration and growth of the tumor spheres.
Keywords	Nasopharyngeal carcinoma ; EVI1 ; miR-96 ; miR-449a ; ICG-001 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Erlotinib sensitivity of MAPK1p.D321N mutation in head and neck squamous cell carcinoma

Hoi-Lam Ngan / Peony Hiu Yan Poon / Yu-Xiong Su / Jason Ying Kuen Chan / Kwok-Wai Lo / Chun Kit Yeung / Yuchen Liu / Eileen Wong / Hui Li / Chin Wang Lau / Wenying Piao / Vivian Wai Yan Lui

npj Genomic Medicine, Vol 5, Iss 1, Pp 1-

2020 Volume 5

Abstract: Abstract Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional ... ...

Abstract	Abstract Head and neck squamous cell carcinoma (HNSCC) lacks predictive biomarkers for drug responses. By targeted sequencing, we identified two MAPK1 mutations in recurrent HNSCC, MAPK1p.D321N, and p.R135K. We previously reported an exceptional erlotinib responder with MAPK1p.E322K. Here, by in silico and drug studies, we determined functions of these two recurrence-associated MAPK1 mutations. Residues D321, R135, and E322 are in 3D proximity. MAPK1p.D321N drives marked in vivo erlotinib sensitivity, while p.R135K’s effect is moderate.
Keywords	Medicine ; R ; Genetics ; QH426-470
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma.

Meng Xu / Chartia Ching-Mei Cheung / Chit Chow / Samantha Wei-Man Lun / Siu-Tim Cheung / Kwok-Wai Lo

PLoS ONE, Vol 11, Iss 6, p e

2016 Volume 0156833

Abstract: BACKGROUND:Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV)-associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid ... ...

Abstract	BACKGROUND:Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV)-associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid residues, which makes it an important regulator in cell survival and apoptosis. In this study, we investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1's potential role as a therapeutic target. METHODS:The expression of PIN1 was examined in a panel of NPC cell lines, xenografts and primary tumors. The functional roles of PIN1 in NPC cells were elucidated by the knockdown and overexpression of PIN1 in in vitro and in vivo nude mice models by siRNA and lenti-viral transfection, respectively. The antitumor effects of the PIN1 inhibitor Juglone in NPC cells were also evaluated. RESULTS:We revealed the consistent overexpression of PIN1 in almost all EBV-associated NPC cell lines, xenografts and primary tumors. PIN1 suppression was capable of inhibiting cyclin D1 expression and activating caspase-3 in NPC cells. It positively regulated NPC cell proliferation, colony formation and anchorage-independent growth. The inhibition of PIN1 suppressed tumor growth in vitro and in vivo. CONCLUSIONS:This study demonstrates the oncogenic role of PIN1 in NPC tumorigenesis, and shows that its overexpression can enhance tumor cell growth via the upregulation of cyclinD1. Our findings inform the development of novel treatments targeting PIN1 for NPC patients.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Dual‐Targeting Peptide‐Guided Approach for Precision Delivery and Cancer Monitoring by Using a Safe Upconversion Nanoplatform

Shuai Zha / Ho‐Fai Chau / Wai Yin Chau / Lai Sheung Chan / Jun Lin / Kwok Wai Lo / William Chi‐Shing Cho / Yim Ling Yip / Sai Wah Tsao / Paul J. Farrell / Liang Feng / Jin Ming Di / Ga‐Lai Law / Hong Lok Lung / Ka‐Leung Wong

Advanced Science, Vol 8, Iss 5, Pp n/a-n/a (2021)

2021

Abstract: Abstract Using Epstein‐Barr virus (EBV)‐induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual‐EBV‐oncoproteins‐targeting pH‐responsive peptide engineering, coating, and guiding approach to achieve precision targeting and ...

Abstract	Abstract Using Epstein‐Barr virus (EBV)‐induced cancer cells and HeLa cells as a comparative study model, a novel and safe dual‐EBV‐oncoproteins‐targeting pH‐responsive peptide engineering, coating, and guiding approach to achieve precision targeting and treatment strategy against EBV‐associated cancers is introduced. Individual functional peptide sequences that specifically bind to two overexpressed EBV‐specific oncoproteins, EBNA1 (a latent cellular protein) and LMP1 (a transmembrane protein), are engineered in three different ways and incorporated with a pH‐sensitive tumor microenvironment (TME)‐cleavable linker onto the upconversion nanoparticles (UCNP) NaGdF4:Yb3+, Er3+@NaGdF4 (UCNP‐Pn, n = 5, 6, and 7). A synergistic combination of the transmembrane LMP1 targeting ability and the pH responsiveness of UCNP‐Pn is found to give specific cancer differentiation with higher cellular uptake and accumulation in EBV‐infected cells, thus a lower dose is needed and the side effects and health risks from treatment would be greatly reduced. It also gives responsive UC signal enhancement upon targeted dual‐protein binding and shows efficacious EBV cancer inhibition in vitro and in vivo. This is the first example of simultaneous imaging and inhibition of two EBV latent proteins, and serves as a blueprint for next‐generation peptide‐guided precision delivery nanosystem for the safe monitoring and treatment against one specific cancer.
Keywords	EBV‐associated cancer imaging ; lanthanide upconversion nanoplatform ; peptide‐guided precision cancer therapy ; pH‐responsive peptide ; selective EBV‐infected cytotoxicity ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification and characterization of a novel Epstein-Barr Virus-encoded circular RNA from LMP-2 Gene

Ke-En Tan / Wei Lun Ng / Georgi K. Marinov / Ken Hung-On Yu / Lu Ping Tan / Ee Shan Liau / Sook Yan Goh / Kok Siong Yeo / Kevin Y. Yip / Kwok-Wai Lo / Alan Soo-Beng Khoo / Lee-Fah Yap / Chee-Kwee Ea / Yat-Yuen Lim

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 15

Abstract: Abstract Epstein-Barr virus (EBV) has been recently found to generate novel circular RNAs (circRNAs) through backsplicing. However, comprehensive catalogs of EBV circRNAs in other cell lines and their functional characterization are still lacking. In ... ...

Abstract	Abstract Epstein-Barr virus (EBV) has been recently found to generate novel circular RNAs (circRNAs) through backsplicing. However, comprehensive catalogs of EBV circRNAs in other cell lines and their functional characterization are still lacking. In this study, we have identified a list of putative EBV circRNAs in GM12878, an EBV-transformed lymphoblastoid cell line, with a significant majority encoded from the EBV latent genes. A novel EBV circRNA derived from the exon 5 of LMP-2 gene which exhibited highest prevalence, was further validated using RNase R assay and Sanger sequencing. This circRNA, which we term circLMP-2_e5, can be universally detected in a panel of EBV-positive cell lines modelling different latency programs. It ranges from lower expression in nasopharyngeal carcinoma (NPC) cells to higher expression in B cells, and is localized to both the cytoplasm and the nucleus. We provide evidence that circLMP-2_e5 is expressed concomitantly with its cognate linear LMP-2 RNA upon EBV lytic reactivation, and may be produced as a result of exon skipping, with its circularization possibly occurring without the involvement of cis elements in the short flanking introns. Furthermore, we show that circLMP-2_e5 is not involved in regulating cell proliferation, host innate immune response, its linear parental transcripts, or EBV lytic reactivation. Taken together, our study expands the current repertoire of putative EBV circRNAs, broadens our understanding of the biology of EBV circRNAs, and lays the foundation for further investigation of their function in the EBV life cycle and disease development.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Preclinical evaluation of ribociclib and its synergistic effect in combination with alpelisib in non-keratinizing nasopharyngeal carcinoma

Chi-Hang Wong / Brigette B. Y. Ma / Connie W. C. Hui / Kwok-Wai Lo / Edwin P. Hui / Anthony T. C. Chan

Scientific Reports, Vol 8, Iss 1, Pp 1-

2018 Volume 8

Abstract: Abstract Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of ... ...

Abstract	Abstract Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a critical role in NPC pathogenesis. This study evaluated the preclinical activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) models. Over 95% cell growth inhibition was observed at 96 hours after ribociclib treatment. (IC50 concentrations: HK1 = 1.42 ± 0.23 µM; HK1-LMP1 = 2.18 ± 0.70 µM and C666-1 = 8.26 ± 0.92 µM). HK1 and C666-1 cells were chosen for analysis of ribociclib on kinase signaling, apoptosis and cell cycle. Treatment with ribociclib for 48 hours consistently showed a dose-dependent reduction in phosphorylated and total RB expression and G1 cycle arrest was only observed. Combining ribociclib with the alpha-specific PI3K inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude mice. The co-treatment induced a significant reduction in tumor volume in both xeno-666 and xeno-2117 compared with ribociclib treatment alone and control (p < 0.01). In summary, ribociclib is active in NPC models and the effect on growth inhibition was augmented when combined with alpelisib. This study supports the clinical evaluation of ribociclib in NPC.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2018-05-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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