Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells

Daker, Maelinda; Bhuvanendran, Saatheeyavaane; Ahmad, Munirah; Takada, Kenzo; Khoo, Alan Soo‐Beng

doi:10.3892/mmr.2012.1253

Cited by 38 publications

(38 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Much like the Wnt response [7,8], an increase in LDs has been correlated with human cancer progression [37], and a causal link was found between LD density and the proliferation of colonic epithelia cells [38]. Moreover, overexpression of genes regulating endocytic uptake of lipids have been linked to the invasiveness of metastatic cancers [39], and more directly, the proliferation of nasopharyngeal carcinoma cells has been show to depend on LDL [40]. We thus speculate that the ability of Wnt to induce LD accumulation is linked with its oncogenic activity: Wnt-dependent regulation of LDs may serve to exert pro-proliferative effects, both in developmental and in pathological contexts.…”

Section: Discussionmentioning

confidence: 99%

Wnt directs the endosomal flux of LDL ‐derived cholesterol and lipid droplet homeostasis

et al. 2015

View full text Add to dashboard Cite

The Wnt pathway, which controls crucial steps of the development and differentiation programs, has been proposed to influence lipid storage and homeostasis. In this paper, using an unbiased strategy based on high-content genome-wide RNAi screens that monitored lipid distribution and amounts, we find that Wnt3a regulates cellular cholesterol. We show that Wnt3a stimulates the production of lipid droplets and that this stimulation strictly depends on endocytosed, LDL-derived cholesterol and on functional early and late endosomes. We also show that Wnt signaling itself controls cholesterol endocytosis and flux along the endosomal pathway, which in turn modulates cellular lipid homeostasis. These results underscore the importance of endosome functions for LD formation and reveal a previously unknown regulatory mechanism of the cellular programs controlling lipid storage and endosome transport under the control of Wnt signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Wnt directs the endosomal flux of LDL ‐derived cholesterol and lipid droplet homeostasis

et al. 2015

View full text Add to dashboard Cite

show abstract

“…NF‐κB physically control the balance of glycolysis and mitochondrial respiration (Mauro et al, ). Increasing evidence indicated EBV LMP1 stimulate aerobic glycolysis in NPC cells by distinct mechanisms (Daker, Bhuvanendran, Ahmad, Takada, & Khoo, ; Jiang et al, ; Lo et al, ; Lo, Lo, Ko, Young, & Dawson, ; Sung, Chen, Liao, & Lee, ; Xiao et al, ). Notably, latency‐associated miRNAs of herpesviruses, such as Kaposi's sarcoma‐associated herpesvirus (KSHV) and EBV, could be transferred to surrounding cells via exosomes to shape it's metabolism toward aerobic glycolysis (Yogev et al, ).…”

Section: Nf‐κb Signaling Determine Ebv‐mediated Metabolic Reprogrammimentioning

confidence: 99%

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

Man

Cai

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Nasopharyngeal carcinoma (NPC) is a unique EBV-associated subtype of head and neck cancer, which has the highest incidence in Southern China and eastern South Asia. The interaction between genetic risk factors and environmental challenge, have been considered to contribute to the development of nasopharyngeal carcinogenesis. Constitutive activation of NF-κB signaling has been seen in NPC tissues and is associated with unfavorable prognosis. Recently, several whole exome sequencing study consistently revealed that high frequency mutations of NF-κB pathway negative regulators is common in nasopharyngeal carcinoma, which reinforce the importance of NF-κB driving oncogenesis. This review focuses on the current state of research in role of NF-κB in NPC carcinogenesis. We summarized the newly identified loss of function (LOF) mutations on NF-κB negative regulators leading to it's activation bypass LMP-1 stimulation. We discussed the critical role of NF-κB activation in immortalization and transformation of nasopharygeal epithelium. We also depicted how NF-κB signaling mediated chronic inflammation contribute to persistent EBV infection, immune evasion of EBV infected cells, metabolic reprogramming, and cancer stem cells (CSCs) formation in NPC. Lastly, we discussed the clinical resonance of targeting NF-κB for NPC precise therapy.

show abstract

“…In addition, NPC accounts for ~50,000 mortalities annually worldwide and ~80,000 novel cases are diagnosed each year (1,2). NPC is a radiosensitive neoplasm, for which radiotherapy (RT) is the primary treatment option.…”

Section: Introductionmentioning

confidence: 99%

PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal carcinoma cells following ionizing radiation, while inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells

Chen

Zhao

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

It was previously reported that poly-(adenosine diphosphate-ribose) polymerase-1 (PARP-1) regulated ionizing radiation (IR)-induced autophagy in CNE-2 human nasopharyngeal carcinoma cells. The present study aimed to investigate whether PARP-1-mediated IR-induced autophagy occurred via activation of the liver kinase B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in CNE-2 cells. In addition, the effect of PARP-1 and AMPK inhibition on the radiation sensitization of CNE-2 cells was investigated. CNE-2 cells were treated with 10 Gy IR in the presence or absence of the AMPK activator 5-amino-1-β-D-ribofuranosyl-1H-imidazole-4-carboxamide (AICAR). In addition, IR-treated CNE-2 cells were transfected with lentivirus-delivered small-hairpin RNA or treated with the AMPK inhibitor Compound C. Western blot analysis was used to assess the protein expression of PARP-1, phosphorylated (p)-AMPK, microtubule-associated protein 1 light chain 3 (LC3)-II and p-P70S6K. Cell viability and clone formation assays were performed to determine the effect of PARP-1 silencing and AMPK inhibition on the radiation sensitization of CNE-2 cells. The results showed that IR promoted PARP-1, p-AMPK and LC3-II protein expression as well as decreased p-P70S6K expression compared with that of the untreated cells. In addition, AICAR increased the expression of p-AMPK and LC3-II as well as decreased p-P70S6K expression compared with that of the IR-only group; however, AICAR did not increase PARP-1 expression. Furthermore, PARP-1 gene silencing decreased the expression of PARP-1, p-AMPK and LC3-II as well as increased p-P70S6K expression. Compound C decreased p-AMPK and LC3-II expression as well as increased p-P70S6K expression; however, Compound C did not increase PARP-1 expression. Western blot analysis detected limited expression of p-LKB1 in all treatment groups. Cell viability and clone formation assays revealed that PARP-1 or AMPK inhibition reduced the proliferation of CNE-2 cells following IR. In conclusion, the present study demonstrated that PARP-1 promoted autophagy via the AMPK/mTOR pathway; in addition, PARP-1 or AMPK inhibition contributed to the radiation sensitization of CNE-2 cells following IR. However, it remains to be elucidated whether PARP-1 is an upstream mediator of the LKB1 pathway in CNE-2 cells following IR.

show abstract

Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells

Cited by 38 publications

References 39 publications

Wnt directs the endosomal flux of LDL ‐derived cholesterol and lipid droplet homeostasis

Wnt directs the endosomal flux of LDL ‐derived cholesterol and lipid droplet homeostasis

Rediscovery of NF‐κB signaling in nasopharyngeal carcinoma: How genetic defects of NF‐κB pathway interplay with EBV in driving oncogenesis?

PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal carcinoma cells following ionizing radiation, while inhibition of autophagy contributes to the radiation sensitization of CNE-2 cells

Contact Info

Product

Resources

About