EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma

Lu, Jinmiao; Tang, Min; Li, Hongde; Xu, Zhijie; Weng, Xiaole; Li, Jiangjiang; Yu, Xinfang; Zhao, Luqing; Liu, Hongwei; Hu, Yongbin; Yang, Lifang; Zhong, Meizuo; Zhou, Jian; Fan, Jia; Bode, Ann M.; Yi, Wei; Gao, Jinghe; Sun, Lun‐Quan; Cao, Yang

doi:10.1016/j.canlet.2016.05.032

Cited by 74 publications

(63 citation statements)

References 49 publications

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“…The final concentrations of DIO, LY294002 and MK2206 used for the stimulation of cells were 10 μM, 20 μM and 10 μM, respectively. Additionly, the radiation processing time we used in this manuscript is 1h, which is in accordance with the previous findings [16]. …”

Section: Methodssupporting

confidence: 89%

Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway

Yan

Xiao

et al. 2017

PLoS ONE

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Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

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Section: Methodssupporting

confidence: 89%

Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway

Yan

Xiao

et al. 2017

PLoS ONE

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“…Moreover, LMP1 reduced the phosphorylation of AMP‐activated protein kinase (AMPK) and changed its subcellular location after irradiation, which appeared to occur through a disruption of the physical interaction between AMPK and DNA‐PK. The decrease in AMPK activity was associated with LMP1‐mediated glycolysis and resistance to apoptosis induced by irradiation . Our recent study showed that the expression level of CPT1A is associated with poor overall survival of NPC patients following radiation treatment.…”

Section: Discussionmentioning

confidence: 93%

PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

Tan

Shi

et al. 2019

Cancer Science

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The PPAR coactivator‐1α (PGC1α) is an important transcriptional co‐activator in control of fatty acid metabolism. Mitochondrial fatty acid oxidation (FAO) is the primary pathway for the degradation of fatty acids and promotes NADPH and ATP production. Our previous study demonstrated that upregulation of carnitine palmitoyl transferase 1 A (CPT1A), the key regulator of FAO, promotes radiation resistance of nasopharyngeal carcinoma (NPC). In this study, we found that high expression of PGC1α is associated with poor overall survival in NPC patients after radiation treatment. Targeting PGC1α could sensitize NPC cells to radiotherapy. Mechanically, PGC1α binds to CCAAT/enhancer binding protein β (CEBPB), a member of the transcription factor family of CEBP, to promote CPT1A transcription, resulting in activation of FAO. Our results revealed that the PGC1α/CEBPB/CPT1A/FAO signaling axis promotes radiation resistance of NPC. These findings indicate that the expression of PGC1α could be a prognostic indicator of NPC, and targeting FAO in NPC with high expression of PGC1α might improve the therapeutic efficacy of radiotherapy.

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“…Also, a negative correlation has been observed between LMP1 expression and AMPK phosphorylation in NPC lesions . LMP1 also negatively regulates AMPK activity by inhibiting DNA‐dependent protein kinase (DNA‐PK) phosphorylation and activity, thereby facilitating LMP1‐mediated glycolysis and resistance to apoptosis induced by irradiation …”

Section: Metabolic Regulators and Pathways Manipulated By γ‐Herpesvirmentioning

confidence: 99%

The role of metabolic reprogramming in γ‐herpesvirus‐associated oncogenesis

Dawson

Young

et al. 2017

Intl Journal of Cancer

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The γ-herpesviruses, EBV and KSHV, are closely associated with a number of human cancers. While the signal transduction pathways exploited by γ-herpesviruses to promote cell growth, survival and transformation have been reported, recent studies have uncovered the impact of γ-herpesvirus infection on host cell metabolism. Here, we review the mechanisms used by γ-herpesviruses to induce metabolic reprogramming in host cells, focusing on their ability to modulate the activity of metabolic regulators and manipulate metabolic pathways. While γ-herpesviruses alter metabolic phenotypes as a means to support viral infection and long-term persistence, this modulation can inadvertently contribute to cancer development. Strategies that target deregulated metabolic phenotypes induced by γ-herpesviruses provide new opportunities for therapeutic intervention.

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EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma

Cited by 74 publications

References 49 publications

Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway

Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway

PGC1α/CEBPB/CPT1A axis promotes radiation resistance of nasopharyngeal carcinoma through activating fatty acid oxidation

The role of metabolic reprogramming in γ‐herpesvirus‐associated oncogenesis

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