LMP1‐positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling

Zhang, Zhibao; Yu, Xuehui; Zhou, Zhuan; Li, Bo; Peng, Jinwu; Wu, Xia; Luo, Xiangjian; Yang, Lifang

doi:10.1002/cam4.2506

Cited by 56 publications

(43 citation statements)

References 40 publications

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“…Further, nasopharyngeal carcinoma cells expressing EBV gene BHRF1 recovered faster after 60 Co radiation with higher cell proliferative rate and colony formation ability, beside a greater tumor formation in nude mice compared to control groups ( 207 ). This is in line with the EBV LMP1-induced proliferation, invasion, apoptosis suppression, and radioresistance in NPC cells ( 208 ).…”

Section: Introductionsupporting

confidence: 76%

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Herbein

Nehme

2020

Front. Oncol.

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Tumors are renowned as intricate systems that harbor heterogeneous cancer cells with distinctly diverse molecular signatures, sizes and genomic contents. Among those various genomic clonal populations within the complex tumoral architecture are the polyploid giant cancer cells (PGCC). Although described for over a century, PGCC are increasingly being recognized for their prominent role in tumorigenesis, metastasis, therapy resistance and tumor repopulation after therapy. A shared characteristic among all tumors triggered by oncoviruses is the presence of polyploidy. Those include Human Papillomaviruses (HPV), Epstein Barr Virus (EBV), Hepatitis B and C viruses (HBV and HCV, respectively), Human T-cell lymphotropic virus-1 (HTLV-1), Kaposi's sarcoma herpesvirus (KSHV) and Merkel polyomavirus (MCPyV). Distinct viral proteins, for instance Tax for HTLV-1 or HBx for HBV have demonstrated their etiologic role in favoring the appearance of PGCC. Different intriguing biological mechanisms employed by oncogenic viruses, in addition to viruses with high oncogenic potential such as human cytomegalovirus, could support the generation of PGCC, including induction of endoreplication, inactivation of tumor suppressors, development of hypoxia, activation of cellular senescence and others. Interestingly, chemoresistance and radioresistance have been reported in the context of oncovirus-induced cancers, for example KSHV and EBV-associated lymphomas and high-risk HPV-related cervical cancer. This points toward a potential linkage between the previously mentioned players and highlights PGCC as keystone cancer cells in virally-induced tumors. Subsequently, although new therapeutic approaches are actively needed to fight PGCC, attention should also be drawn to reveal the relationship between PGCC and oncoviruses, with the ultimate goal of establishing effective therapeutic platforms for treatment of virus-associated cancers. This review discusses the presence of PGCCs in tumors induced by oncoviruses, biological mechanisms potentially favoring their appearance, as well as their consequent implication at the clinical and therapeutic level.

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Section: Introductionsupporting

confidence: 76%

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Herbein

Nehme

2020

Front. Oncol.

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“…The expressions of cleaved caspase‐3, caspase‐8, caspase‐9, and PARP were progressively upregulated with the increase in CA dosage in both HONE‐1 (Figure 4A,B) and NPC‐39 cell lines (Figure 4C,D). Moreover, numerous studies have speculated that the molecular mechanism of the MAPK pathways participates in cell apoptosis . Thus, the effect of CA on the phosphorylation of MAPK, the upstream pathway for caspases, was also tested.…”

Section: Resultsmentioning

confidence: 99%

Cantharidic acid induces apoptosis in human nasopharyngeal carcinoma cells through p38‐mediated upregulation of caspase activation

Chen

Lin

et al. 2020

Environmental Toxicology

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Cantharidic acid (CA) is the hydrolysis product of the acid anhydride cantharidin, which is a natural toxin secreted by several species of blister beetles. Several studies have indicated that as an inhibitor of protein phosphatase 2 (PP2A), CA induces apoptosis in various human cancer cells. However, the effect of CA on human nasopharyngeal carcinoma (NPC) cells and the underlying pathways have not been addressed. In our current study, we tested the hypothesis that CA treatment reduces the viability of human NPC cells (HONE‐1, NPC‐39, and NPC‐BM) by inducing apoptosis. Results indicated that CA markedly reduced cell viability, which was revealed by the upregulation of caspase activation in extrinsic and intrinsic apoptosis pathways as well as the upregulation of extracellular‐signal‐regulated kinase 1/2 (ERK1/2), p38, and c‐Jun N‐terminal kinase 1/2 (JNK1/2) pathways. Coadministration of a p38 inhibitor (SB203580) with CA abolished the activation of caspase proteins. These findings indicated that CA treatment leads to apoptosis in human NPC cells through the upregulation of caspase activation, mediated particularly by the p38 pathway. Hence, CA is a promising therapeutic agent for human NPC.

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“…[25][26][27] Zhang et al found that exosomes derived from latent membrane protein 1-positive NPC cells could induce recipient NPC cell proliferation and invasion and suppress apoptosis, especially promote radioresistance. 28 Thus, we suppose that circMYC is a potential target to overcome radioresistance in patients with NPC.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma

Luo

Liu

et al. 2020

Head & Neck

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Background: The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC. Methods: The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2 0-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed. Results: Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and lossfunctional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy. Conclusion: circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.

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LMP1‐positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling

Cited by 56 publications

References 40 publications

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Polyploid Giant Cancer Cells, a Hallmark of Oncoviruses and a New Therapeutic Challenge

Cantharidic acid induces apoptosis in human nasopharyngeal carcinoma cells through p38‐mediated upregulation of caspase activation

Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma

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