Irciniastatin A, a pederin-type translation inhibitor, promotes ectodomain shedding of cell-surface tumor necrosis factor receptor 1

Irciniastatin A is a pederin-type marine product that potently inhibits translation. We have recently shown that irciniastatin A induces ectodomain shedding of tumor necrosis factor (TNF) receptor 1 with slower kinetics than other translation inhibitors. In human lung carcinoma A549 cells, irciniastatin A induced a marked and sustained activation of extracellular signal-regulated kinase (ERK) and induced little activation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK). Moreover, the TNF receptor 1 shedding induced by irciniastatin A was blocked by the MAP kinase/ERK kinase inhibitor U0126, but not by the p38 MAP kinase inhibitor SB203580 or the JNK inhibitor SP600125. Thus unlike other translation inhibitors that trigger ribotoxic stress response, our results show that irciniastatin A is a unique translation inhibitor that induces a potent and sustained activation of the ERK pathway, and thereby promotes the ectodomain shedding of TNF receptor 1 in A549 cells.Key words irciniastatin A; extracellular signal-regulated kinase; translation inhibitor; tumor necrosis factor receptor 1; ribotoxic stress response; p38 mitogen-activated protein kinase Irciniastatin A, also known as psymberin (Fig. 1A), is a marine natural product originally isolated from the marine sponges Ircinia ramose and Psammocinia.

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“…As recently reported, 15) irciniastatin A increased the amount of soluble TNF receptor 1 in the culture medium for 3 h (Fig. 1B).…”

Section: Resultssupporting

confidence: 65%

“…[12][13][14] Moreover, we have recently reported that irciniastatin A induced the ectodomain shedding of TNF receptor 1 with slower kinetics than the translation inhibitors. 15) Some types of translation inhibitors are known to trigger ribotoxic stress response.…”

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confidence: 99%

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Quach

Hirano

Fukuhara

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Furthermore, several studies have demonstrated that the microenvironment is capable of regulating cancer cell stemness or drug resistance through signaling pathway activation . However, traditional cancer treatments focus on inhibiting tumor cell growth but ignoring the tumor microenvironment elements . Many studies have attempted to reverse drug resistance through various strategies, including the combination of 2 or more anticancer therapeutic agents, inhibitors of ABC transporters, or application of chemosensitizers, which has been proven to be able to reverse drug resistance and inhibit tumor growth in the early stages.…”

Section: Discussionmentioning

confidence: 99%

Reverse of non‐small cell lung cancer drug resistance induced by cancer‐associated fibroblasts via a paracrine pathway

et al. 2018

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The tumor microenvironment orchestrates the sustained growth, metastasis and recurrence of cancer. As an indispensable component of the tumor microenvironment, cancer‐associated fibroblasts (CAF) are considered as an essential synthetic machine producing various tumor components, leading to cancer sustained stemness, drug resistance and tumor recurrence. Here, we developed a sustainable primary culture of lung cancer cells fed with lung cancer‐associated fibroblasts, resulting in enrichment and acquisition of drug resistance in cancer cells. Moreover, IGF2/AKT/Sox2/ABCB1 signaling activation in cancer cells was observed in the presence of CAF, which induces upregulation of P‐glycoprotein expression and the drug resistance of non‐small cell lung cancer cells. Our results demonstrated that CAF cells constitute a mechanism for cancer drug resistance. Thus, traditional chemotherapy combined with insulin‐like growth factor 2 (IGF2) signaling inhibitor may present an innovative therapeutic strategy for non‐small cell lung cancer therapy.

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“…Particular types of translation inhibitors (e.g., anisomycin, glutarimides, and triene-ansamycins) induce the activation of ERK and p38 MAP kinase via a ribotoxic stress response [14,15]. We previously reported that translation inhibitors (e.g., acetoxycycloheximide, cytotrienin A, deoxynivalenol, and irciniastatin A) promoted TACE-dependent TNF-R1 ectodomain shedding by activating ERK and p38 MAP kinase [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Isopanduratin A Inhibits Tumor Necrosis Factor (TNF)-α-Induced Nuclear Factor κB Signaling Pathway by Promoting Extracellular Signal-Regulated Kinase-Dependent Ectodomain Shedding of TNF Receptor 1 in Human Lung Adenocarcinoma A549 Cells

Moriwaki

Tanigaki

Miyake

et al. 2021

BioChem

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Tumor necrosis factor α (TNF-α) induces the nuclear factor κB (NF-κB) signaling pathway via TNF receptor 1 (TNF-R1). We recently reported that isopanduratin A inhibited the TNF-α-induced NF-κB signaling pathway in human lung adenocarcinoma A549 cells. In the present study, we found that isopanduratin A did not inhibit the interleukin-1α-induced NF-κB signaling pathway in A549 cells. Isopanduratin A down-regulated the expression of TNF-R1 in these cells. We also revealed that isopanduratin A down-regulated the cell surface expression of TNF-R1 by promoting the cleavage of TNF-R1 into its soluble forms. TAPI-2, an inhibitor of TNF-α-converting enzyme, suppressed the inhibitory activity of isopanduratin A against the TNF-α-induced activation of NF-κB. The mitogen-activated protein (MAP) kinase/extracellular signal-regulated kinase (ERK) kinase inhibitor U0126, but not the p38 MAP kinase inhibitor SB203580, blocked the ectodomain shedding of TNF-R1 induced by isopanduratin A. Consistent with this result, isopanduratin A induced the rapid phosphorylation of ERK, but not p38 MAP kinase. Isopanduratin A also promoted the phosphorylation of eukaryotic initiation factor 2α (eIF2α). The present results indicate that isopanduratin A inhibits TNF-α-induced NF-κB signaling pathway by promoting ERK-dependent ectodomain shedding of cell surface TNF-R1, and also decreases cellular TNF-R1 levels through the phosphorylation of eIF2α in A549 cells.

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Irciniastatin A, a pederin-type translation inhibitor, promotes ectodomain shedding of cell-surface tumor necrosis factor receptor 1

Cited by 8 publications

References 18 publications

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Irciniastatin A Induces Potent and Sustained Activation of Extracellular Signal-Regulated Kinase and Thereby Promotes Ectodomain Shedding of Tumor Necrosis Factor Receptor 1 in Human Lung Carcinoma A549 Cells

Reverse of non‐small cell lung cancer drug resistance induced by cancer‐associated fibroblasts via a paracrine pathway

Isopanduratin A Inhibits Tumor Necrosis Factor (TNF)-α-Induced Nuclear Factor κB Signaling Pathway by Promoting Extracellular Signal-Regulated Kinase-Dependent Ectodomain Shedding of TNF Receptor 1 in Human Lung Adenocarcinoma A549 Cells

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