Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90-ERK pathway mediated DNA repair in esophageal squamous cell carcinoma

Sun, Yulin; Zhai, Linhui; Ma, Shouzhi; Zhang, Chengpu; Zhao, Lina; Li, Ning; Xu, Yang; Zhang, Tao; Guo, Zhen; Zhang, Heng; Xu, Ping; Zhao, Xiaohang

doi:10.1016/j.canlet.2018.01.022

Cited by 37 publications

(35 citation statements)

References 39 publications

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“…U0126, which is predicted as ‘Inhibited’, is the MEK inhibitor of upstream molecules in ERK1/2 27 . As activated cancer-related or angiogenesis-related molecules, VEGF-A, HSP90 28 and EDN1 29 were predicted (Table 1 ). Sulforaphane, which is predicted as ‘Inhibited’, is known as an angiogenesis inhibitor 30 .…”

Section: Discussionmentioning

confidence: 99%

Exosomes released from pancreatic cancer cells enhance angiogenic activities via dynamin-dependent endocytosis in endothelial cells in vitro

Chiba

Kubota

Sato

et al. 2018

Sci Rep

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Pancreatic cancer has the lowest 5 year survival rate among all cancers. Several extracellular factors are involved in the development and metastasis of pancreatic cancer to distant organs. Exosomes are lipid-bilayer, membrane-enclosed nanoparticles that are recognised as important mediators of cell-to-cell communications. However, the role of exosomes released from pancreatic cancer cells in tumour micro-environment remains unknown. Here, we show that exosomes released from pancreatic cancer PK-45H cells activate various gene expressions in human umbilical vein endothelial cells (HUVECs) by in vitro analyses. In addition, these exosomes released from PK-45H cells promote phosphorylation of Akt and ERK1/2 signalling pathway molecules and tube formation via dynamin-dependent endocytosis in HUVECs. Our findings suggested that exosomes released from pancreatic cancer cells may act as a novel angiogenesis promoter.

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Section: Discussionmentioning

confidence: 99%

Exosomes released from pancreatic cancer cells enhance angiogenic activities via dynamin-dependent endocytosis in endothelial cells in vitro

Chiba

Kubota

Sato

et al. 2018

Sci Rep

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“…Recent studies have shown that treatment with hypomethylating agents restores silenced RIPK3 expression and increases sensitivity to chemotherapeutic agents in an RIPK3-dependent manner (6). Upregulation of silenced RIPK3 expression also restores cisplatin sensitivity, suggesting that RIPK3 contributes to cisplatin chemosensitivity (7). Based on these findings, we examined the role of RIPK3 as a potential predictive biomarker of cisplatin-based adjuvant chemotherapy in patients who previously underwent surgical resection of lung adenocarcinoma (LUAD).…”

Section: Introductionmentioning

confidence: 97%

Receptor-interacting protein kinase 3 as a predictive adjuvant chemotherapy marker after lung adenocarcinoma resection

et al. 2019

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Background: This study assessed the predictive value of receptor-interacting protein kinase 3 (RIPK3) expression and its correlation with clinicopathological characteristics, disease-free survival, and overall survival of patients with cisplatin-based adjuvant chemotherapy after lung adenocarcinoma resection. Methods: This study included 50 patients who underwent cisplatin-based adjuvant chemotherapy after lung adenocarcinoma (stage IB-IIIA) resection. Immunohistochemical analysis was performed by probing tumor tissue microarrays with anti-RIPK3 antibody. Results: High RIPK3 expression was detected in 24 (48.0%) of the 50 patients. Moreover, high RIPK3 expression was associated with a prolonged disease-free survival (P=0.015) but not with a prolonged overall survival (P=0.109) of the patients who underwent cisplatin doublet therapy after lung adenocarcinoma resection. We also examined whether RIPK3 expression was associated with prognosis based on chemotherapeutic response and found that patients with low RIPK3 expression showed a higher tendency of developing a progressive disease [14/26 (53.8%) patients] than patients with high RIPK3 expression [6/24 (25.0%) patients] (P=0.03). Results of Cox univariate proportional hazards regression model showed that age, N stage, and high RIPK3 expression (P=0.04) were associated with the prolonged disease-free survival of the patients who underwent cisplatin-based adjuvant chemotherapy after lung adenocarcinoma resection. Conclusions: These results suggest that RIPK3 overexpression is a potential biomarker to identify patients with lung adenocarcinoma who can benefit the most from cisplatin-based adjuvant chemotherapy after complete adenocarcinoma resection.

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“…Necroptosis is triggered by several types of stimuli, including abnormal cellular metabolism, activation of receptors by ligands such as tumor necrosis factor-TNF, interferon, Toll-like receptor ligands, and anticancer substances. The most well-studied mechanism is triggered by TNF, through recruitment of RIPK1 (receptor interacting protein kinase 1) and inhibition of caspase 8 (Su et al 2016;Sun et al 2018). RIPK1 has important kinase-dependent and scaffolding functions that inhibit or trigger necroptosis resulting in expulsion of cellular contents to the extracellular space (Galluzzi et al 2011).…”

Section: Introductionmentioning

confidence: 99%

The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells

et al. 2018

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Antimicrobial peptides present a broad spectrum of therapeutic applications, including their use as anticancer peptides. These peptides have as target microbial, normal, and cancerous cells. The oncological properties of these peptides may occur by membranolytic mechanisms or non-membranolytics. In this work, we demonstrate for the first time the cytotoxic effects of the cationic alpha-helical antimicrobial peptide LyeTx I-b on glioblastoma lineage U87-MG. The anticancer property of this peptide was associated with a membranolytic mechanism. Loss of membrane integrity occurred after incubation with the peptide for 15 min, as shown by trypan blue uptake, reduction of calcein-AM conversion, and LDH release. Morphological studies using scanning electron microscopy demonstrated disruption of the plasma membrane from cells treated with LyeTx I-b, including the formation of holes or pores. Transmission electron microscopy analyses showed swollen nuclei with mild DNA condensation, cell volume increase with an electron-lucent cytoplasm and organelle vacuolization, but without the rupture of nuclear or plasmatic membranes. Morphometric analyses revealed a high percentage of cells in necroptosis stages, followed by necrosis and apoptosis at lower levels. Necrostatin-1, a known inhibitor of necroptosis, partially protected the cells from the toxicity of the peptide in a concentration-dependent manner. Imaging flow cytometry confirmed that 59% of the cells underwent necroptosis after 3-h incubation with the peptide. It is noteworthy that LyeTx I-b showed only mild cytotoxicity against normal fibroblasts of human and monkey cell lines and low hemolytic activity in human erythrocytes. All data together point out the anticancer potential of this peptide.

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Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90-ERK pathway mediated DNA repair in esophageal squamous cell carcinoma

Cited by 37 publications

References 39 publications

Exosomes released from pancreatic cancer cells enhance angiogenic activities via dynamin-dependent endocytosis in endothelial cells in vitro

Exosomes released from pancreatic cancer cells enhance angiogenic activities via dynamin-dependent endocytosis in endothelial cells in vitro

Receptor-interacting protein kinase 3 as a predictive adjuvant chemotherapy marker after lung adenocarcinoma resection

The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells

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