Inhibition of MKK7–JNK by the TOR Signaling Pathway Regulator-Like Protein Contributes to Resistance of HCC Cells to TRAIL-Induced Apoptosis

Song, In Sung; Jun, Soo Young; Na, Hee–Jun; Kim, Hyun-taek; Jung, So Young; Ha, Ga Hee; Park, Young–Ho; Long, Liang Zhe; Yu, Dae‐Yeul; Kim, Jin Man; Kim, Joo Heon; Ko, Jeong–Heon; Kim, Cheol–Hee; Kim, Nam–Soon

doi:10.1053/j.gastro.2012.07.103

Cited by 45 publications

(53 citation statements)

References 32 publications

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“…16, 38 These reports confirm our finding that HDAC8-dependent repression of TIPRL expression by cAMP signaling contributes to the augmentation of cisplatin-induced apoptosis. TIPRL also influences the phosphorylation state of a specific protein substrate of ATM- and Rad3-related (ATR) kinases, which implies a role for TIPRL in DNA repair 39 that may contribute to the modulation of apoptosis.…”

Section: Discussionsupporting

confidence: 87%

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cAMP signaling increases histone deacetylase 8 expression via the Epac2–Rap1A–Akt pathway in H1299 lung cancer cells

Park

Juhnn

2017

Exp Mol Med

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This study was performed to investigate the signaling pathway that mediates cyclic AMP (cAMP)-induced inhibition of histone deacetylase 8 (HDAC8) degradation, and the effect and underlying mechanisms of the resulting increase in HDAC8 expression on cisplatin-induced apoptosis in lung cancer cells. cAMP signaling increased HDAC8 expression via a protein kinase A (PKA)-independent pathway in H1299 non-small cell lung cancer cells. However, treatment with a selective activator of an exchange protein that was activated by cAMP (Epac) increased HDAC8 expression, and Epac2 inhibition abolished the isoproterenol (ISO)-induced increase in HDAC8 expression. ISO and the Epac activator activated Rap1, and Rap1A activation increased HDAC8 expression; moreover, inhibition of Rap1A with a dominant negative Rap1A or by shRNA-mediated knockdown abolished the ISO-induced increase in HDAC8 expression. Activation of cAMP signaling and Rap1A decreased the activating phosphorylation of Akt. Akt inhibition with a pharmacological inhibitor or expression of a dominant negative Akt inhibited the MKK4/JNK pathway and increased HDAC8 expression. The Akt inhibitor-induced increase in HDAC8 expression was abolished by pretreatment with proteasomal or lysosomal inhibitors. The ISO treatment increased cisplatin-induced apoptosis, which was abolished by HDAC8 knockdown. Exogenous HDAC8 expression increased cisplatin-induced apoptosis and decreased TIPRL expression, and the knockdown of TIPRL increased the apoptosis of cisplatin-treated cells. The ISO treatment decreased cisplatin-induced transcription of the TIPRL gene in a HDAC8-dependent manner. In conclusion, the Epac–Rap1–Akt pathway mediates cAMP signaling-induced inhibition of JNK-dependent HDAC8 degradation, and the resulting HDAC8 increase augments cisplatin-induced apoptosis by repressing TIPRL expression in H1299 lung cancer cells.

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Section: Discussionsupporting

confidence: 87%

“…16 We found that its expression was reduced by cAMP signaling (our unpublished data). Treatment with cisplatin increased the TIPRL protein levels; exogenous HDAC8 expression decreased cisplatin-induced TIPRL protein expression and increased cisplatin-induced cleavage of caspase-3 and caspase-9 (Figure 6d).…”

Section: Resultsmentioning

confidence: 77%

cAMP signaling increases histone deacetylase 8 expression via the Epac2–Rap1A–Akt pathway in H1299 lung cancer cells

Park

Juhnn

2017

Exp Mol Med

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“…The study of Szu-ying Chen et al demonstrated that autophagic cell death and ROS generation could be attenuated by inhibiting ERK with U0126 [43]. Besides, it has been reported that inhibiting JNK by the TOR signaling pathway regulator-like (TIPRL) protein decreased the apoptosis induced by TRAIL in hepatocellular carcinoma (HCC) cells [71]. Consistent with the results of these studies, our data revealed that using SP600125, the pharmacological inhibitor of JNK, resulted in the weakening of autophagy and apoptosis in the U251 cells treated with AgNPs and radiation.…”

Section: Erk and Jnk Signaling Pathways And Autophagy/radio Sensitizingmentioning

confidence: 99%

Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Wu¹,

Lin²,

Liu³

et al. 2015

Biomaterials

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“…We previously confirmed that the xenografts inoculated onto the right flanks of nude mice retained the genomic characteristics of hepatocellular carcinoma 7 . Having identified growing mass of hepatocellular carcinoma, we performed PDT twice and examined its efficacy in treatment of cancer by comparing volume of tumor mass among groups, counting alive individuals in each group, carrying out Western blot and TUNEL assay to quantify apoptosis-related proteins and degree of DNA fragmentation, respectively.…”

Section: Discussionmentioning

confidence: 75%

Pu-18-N-butylimide-NMGA-GNP conjugate is effective against hepatocellular carcinoma

Kwon

Song

Kim

et al. 2013

Integrative Medicine Research

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BackgroundPhotodynamic therapy (PDT) is a new modality in the treatment of cancer. This study thus aims to examine whether the PDT is effective against in vivo hepatocellular carcinoma.MethodsIn vivo efficacy of PDT on hepatocellular carcinoma was tested in xenografted mice with human hepatocellular carcinoma cell lines (Huh7) by utilizing a gold nanoparticles (GNPs) conjugate of new photosensitizer (PS), purpurin-18-N-butylimide-N-methyl-D-glucamine (Pu-18-N-butylimide-NMGA). The conjugate (PS-GNPs) was synthesized from the reaction between Pu-18-N-butylimide-NMGA and chloroauric acid (HAuCl4). Mice were arbitrarily assigned into one of three groups. First group received saline alone, second group received PS-GNPs alone, and the last group received both PS-GNPs and irradiation. PS-GNPs was injected directly into the tumor mass and irradiations were performed 24 hours after injection of PS-GNPs.ResultsTumor volume was significantly smaller in the group which received both PS-GNPs and irradiation compared with other two groups. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed that the group which received both PS-GNPs and irradiation showed larger amount of apoptotic protein and DNA fragmentation compared with other two groups.ConclusionThis study suggests that Pu-18-N-butylimide-NMGA-GNP conjugate is an effective agent for PDT in the treatment of hepatocellular carcinoma.

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Inhibition of MKK7–JNK by the TOR Signaling Pathway Regulator-Like Protein Contributes to Resistance of HCC Cells to TRAIL-Induced Apoptosis

Cited by 45 publications

References 32 publications

cAMP signaling increases histone deacetylase 8 expression via the Epac2–Rap1A–Akt pathway in H1299 lung cancer cells

cAMP signaling increases histone deacetylase 8 expression via the Epac2–Rap1A–Akt pathway in H1299 lung cancer cells

Is the autophagy a friend or foe in the silver nanoparticles associated radiotherapy for glioma？

Pu-18-N-butylimide-NMGA-GNP conjugate is effective against hepatocellular carcinoma

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