PPP3CB contributes to poor prognosis through activating nuclear factor of activated T‐cells signaling in neuroblastoma

Shakhova, Irina; Li, Yuanyuan; Fan, Yuding; Kaneko, Yoshiki; Nakamura, Yohko; Ohira, Miki; Izumi, Hideki; Mae, Takao; Варфоломеева, С. Р.; Rumyantsev, A.G.; Nakagawara, Akira

doi:10.1002/mc.22939

Cited by 9 publications

(8 citation statements)

References 25 publications

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“…The analysis results of Kaplan-Meier Plotter and SurvExpress showed that high expression of PPP3CB was associated with worse survival in various tumors such as bladder carcinoma, ovarian cancer, gliomas, and glioblastoma (Figure A3). Similar to the with bioinformatic results, previous research found that high PPP3CB expression was an independent indicator predicting poor prognosis of neuroblastoma (NB) [17]. These results indicate that PPP3CB may be a crucial indicator in the diagnosis or prognosis of cancer.…”

Section: Resultssupporting

confidence: 82%

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth

Chen

Liu

et al. 2019

IJMS

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PPP3CB belongs to the phosphoprotein phosphatases (PPPs) group. Although the majority of the PPP family play important roles in the epithelial-to-mesenchymal transition (EMT) of tumor cells, little is known about the function of PPP3CB in the EMT process. Here, we found PPP3CB had high expression in kidney mesenchymal-like cells compared with kidney epithelial-like cells. Knock-down of PPP3CB downregulated epithelial marker E-cadherin and upregulated mesenchymal marker Vimentin, promoting the transition of cell states from epithelial to mesenchymal and reorganizing the actin cytoskeleton which contributed to cell migration. Conversely, overexpression of PPP3CB reversed EMT and inhibited migration of tumor cells. Besides, in vitro and in vivo experiments indicated that the loss of PPP3CB suppressed the tumor growth. However, the deletion of the phosphatase domain of PPP3CB showed no effect on the expression of E-cadherin, migration, and G401 cell proliferation. Together, we demonstrate that PPP3CB inhibits G401 cell migration through regulating EMT and promotes cell proliferation, which are both associated with the phosphatase activity of PPP3CB.

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Section: Resultssupporting

confidence: 82%

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth

Chen

Liu

et al. 2019

IJMS

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“…Calcineurin-NFATc3 pathway plays a critical role in the pathogenesis of multiple tumors [18,19], which could be activated by calcium. As TRPM8 is a calcium-permeable channel, we speculated PD-L1 might be downstream of TRPM8-calcineurin-NFATc3 pathway.…”

Section: Resultsmentioning

confidence: 99%

“…It is well-known that calcineurin is downstream of calcium signaling, which induces dephosphorylation and activation of transcription factor NFAT [28,29]. Plenty of evidence has reported that calcineurin-NFAT signaling pathway contributes to the development and progression of tumors [18,19,28,29]. Calcineurin is specifically modulated by calcium and calmodulin [29].…”

Section: Discussionmentioning

confidence: 99%

“…It has been revealed that dysfunction of cytochrome c oxidase complex-mediated calcium-calcineurin activation is positively related to the progression of esophageal cancer [30], which displays the similar results as we did. A recent research showed that calcineurin-NFATc3 inhibition by calcineurin inhibitor treatment restrained cell proliferation and increased apoptosis of neuroblastoma cells [19]. Liu et al [18] reported that NFATc3 activation could be mediated by Notch1, which accelerated aggressiveness of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

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TRPM8 facilitates proliferation and immune evasion of esophageal cancer cells

Lan

Zhao

Song³

et al. 2019

Bioscience Reports

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Correspondence: Xiaojun Liu (ergesulju2012@163.com)Esophageal cancer is seen with increasing incidence, but the underlying mechanism of esophageal cancer is still unknown. Transient receptor potential melastatin (TRPM) is non-selective cation channels. It has been verified that TRPM channels play crucial roles in development and progression of multiple tumors. Increasing studies have shown that TRPM8, a member of TRPM channels, promotes growth of tumors. However, it is still unclear whether TRPM8 has biological effect on esophageal cancer. In the current work, we found that TRPM8 was overexpressed in esophageal cancer samples and cell lines. Further investigation revealed that TRPM8 promoted proliferation of esophageal cancer cells. Next, the co-incubation assay including EC109 cells and CD8 + T cells revealed that TRPM8 overexpression and TRPM8 agonist reduced the cytotoxic effect of CD8 + T cell on esophageal cancer cells. Finally, we explored the mechanism and found that calcineurin-nuclear factor of activated T cells 3 (NFATc3) pathway contributed to the expression of programmed death ligand 1 (PD-L1) induced by TRPM8 overexpression and TRPM8 agonist, which might lead to immune evasion of esophageal cancer cells. These findings uncovered the crucial role of TRPM8 in the pathogenesis of esophageal cancer.

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“…High PPP3CB expression was an independent indicator predicting poor prognosis of neuroblastoma (NB) [38]. PPP3CB contributes to poor prognosis through activating nuclear factor of activated T-cells signaling in NB.…”

Section: Discussionmentioning

confidence: 99%

Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

Ye²,

Song³

et al. 2020

Preprint

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Background: Cephalosporin antibiotics can drastically upregulate the expression of HMOX1 in nasopharyngeal carcinoma cells. HMOX1 has dual role in cancer cells, and is involved in chemoresistance. Cephalosporin antibiotics are widely used in the treatment of bacteria infectious diseases in cancer patients. Whether they affect the efficacy of chemotherapy is unknown. Methods: Comparisons between cefotaxime and the combination of cefotaxime and cisplatin were carried out throughout the study. Cell viability was detected by MTT method. Influence on clone formation of cancer cells was investigated by plate clone formation assay. The in vivo anticancer effect was determined via cancer xenograft in mice. Flow cytometry analysis was used to detect the apoptosis. Microarray gene expression profiling was analyzed using Gene Ontology analysis, and the differential genes were validated by RT-qPCR. Results: Cefotaxime specifically, selectively and synergistically enhanced the anticancer efficacy of cisplatin in nasopharyngeal carcinoma both in vitro and in vivo without increasing the toxicity, but it inhibited the cytotoxic effects of cisplatin in other cancers. Combination of cefotaxime and cisplatin significantly regulated 5 genes in direction favoring the enhancement of anticancer efficacy; of which, THBS1 and LAPTM5 were upregulated; PPP3CB, STAG1 and NCOA5 were downregulated jointly. HMOX1 contributes to the anticancer efficacy in combination group. Upregulated genes significantly modulated 18 apoptotic pathways, downregulated genes mainly affected assembly of genetic materials. Conclusion: Cephalosporin antibiotics are excellent and safe sensitizers of conventional chemotherapy in the treatment of nasopharyngeal carcinoma, but should be carefully used in other cancers.

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PPP3CB contributes to poor prognosis through activating nuclear factor of activated T‐cells signaling in neuroblastoma

Cited by 9 publications

References 25 publications

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth

PPP3CB Inhibits Migration of G401 Cells via Regulating Epithelial-to-Mesenchymal Transition and Promotes G401 Cells Growth

TRPM8 facilitates proliferation and immune evasion of esophageal cancer cells

Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

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