mTOR Signaling Pathway in Cancer Targets Photodynamic Therapy In Vitro

Ayuk, Sandra M.; Abrahamse, Heidi

doi:10.3390/cells8050431

Cited by 26 publications

(17 citation statements)

References 132 publications

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“…In our phosphoproteomic profile, phosphorylation of heat shock protein HSP 90-alpha (HSP90AA1) at serine 231 was also identified with 11.06 fold-changed upon silencing of ZNF322A, which may contribute to autophagy, however the phosphosite-specific antibody has not yet been established. As previously reported, ZNF322A may act as regulator in gene transcription mediated by the MAPK signaling pathways [60]. Consistent with our findings that siZNF322A upregulated the phosphorylation of HSP27 and MAPKAPK2, participating in p38 MAPK pathway which is responsible for the autophagosome formation.…”

Section: Discussionsupporting

confidence: 93%

ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer

et al. 2020

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Background: ZNF322A is an oncogenic transcription factor that belongs to the Cys2His2-type zinc-finger protein family. Accumulating evidence suggests that ZNF322A may contribute to the tumorigenesis of lung cancer, however, the ZNF322A-mediated downstream signaling pathways remain unknown. Methods: To uncover ZNF322A-mediated functional network, we applied phosphopeptide enrichment and isobaric labeling strategies with mass spectrometry-based proteomics using A549 lung cancer cells, and analyzed the differentially expressed proteins of phosphoproteomic and proteomic profiles to determine ZNF322A-modulated pathways. Results: ZNF322A highlighted a previously unidentified insulin signaling, heat stress, and signal attenuation at the posttranslational level. Consistently, protein-phosphoprotein-kinase interaction network analysis revealed phosphorylation of IRS1 and HSP27 were altered upon ZNF322A-silenced lung cancer cells. Thus, we further investigated the molecular regulation of ZNF322A, and found the inhibitory transcriptional regulation of ZNF322A on PIM3, which was able to phosphorylate IRS1 at serine 1101 in order to manipulate glucose uptake via the PI3K/AKT/mTOR signaling pathway. Moreover, ZNF322A also affects the unfolded protein response by phosphorylation of HSP27 S82 and eIF2a S51 , and triggers autophagosome formation in lung cancer cells. Conclusions: These findings not only give new information about the molecular regulation of the cellular proteins through ZNF322A at the post-translational level, but also provides a resource for the study of lung cancer therapy.

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Section: Discussionsupporting

confidence: 93%

ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer

et al. 2020

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“…The PI3K/AKT pathway is a regulator of aerobic glycolysis and central glucose metabolism 124 . It confer advantages on MDR due to the acidification of the intracellular microenvironment, which may reduce drug absorption and efficiency, and/or an increase in intermediate metabolites 125,126 . Because cell growth depends on the biosynthesis of cellular building blocks produced by metabolic intermediates, it is easy to understand the seemingly contradictory use of this fuel 127 .…”

Section: Bcrpmentioning

confidence: 99%

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

et al. 2020

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Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.

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“…Thus, we found that depletion of linc00342 retarded cell proliferation, accelerated cell apoptosis, and signi cantly reduced migration and invasion ability in KIRC cells. KEGG analysis showed linc00342-related genes were enriched in several important signaling pathways -MAPK, mTOR, insulin, NOD-like receptor, Wnt, and GnRH -that are reported to play key roles in many malignancies [27][28][29][30][31][32]. The effect of these KEGG pathways on the progress of KICC was not explored in our current study.…”

Section: Discussionmentioning

confidence: 70%

Linc00342 serves as a diagnostic and prognostic biomarker in Kidney Renal Clear Cell Carcinoma:A Comprehensive Study Based on Data mining, Clinical Analysis, and in vitro Validation

Guan

Ping

2020

Preprint

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Background: Kidney renal clear cell carcinoma (KIRC), as the most common type of renal cancer, has a high mortality and recurrence rate due to the fact that many patients are in advanced stage at the time of consultation. Finding a biological marker for early-stage KIRC has become a top priority. Recently, accumulating studies have shown that lncRNA can serve as a target for diagnosis and prognosis of malignancy. However, the involvement and mechanism of linc00342 has never been researched in KIRC. The aim of this study was to investigate the diagnostic and prognostic value of linc00342 in KIRC, and to explore the effects of linc00342 on the biological functions of KIRC cells.Methods: We downloaded the linc00342 expression data and clinical information of KIRC from the TCGA database and constructed a prognostic prediction model. In vitro, the effect of knocking down linc00342 on KIRC cell proliferation, apoptosis, metastasis, and invasion was measured by colony-formation assay, flow cytometric analysis, wound-healing assay and Transwell assay, respectively.Results: Our nomogram predictive model suggested linc00342 can serve as an independent prognostic factor for KIRC. GO functional analysis and KEGG pathway analysis showed linc00342 was involved in various biological functions of KIRC, and experiments in vitro verified this. In vitro, linc00342 was overexpressed in KIRC cells as shown by RT-qPCR. Moreover, we found that linc00342 can inhibit cell apoptosis and promote cell proliferation, invasion, and migration.Conclusions: Our study is the first to examine the diagnostic and prognostic value of linc00342 in KIRC and provides new ideas for the treatment of KIRC.

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mTOR Signaling Pathway in Cancer Targets Photodynamic Therapy In Vitro

Cited by 26 publications

References 132 publications

ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer

ZNF322A-mediated protein phosphorylation induces autophagosome formation through modulation of IRS1-AKT glucose uptake and HSP-elicited UPR in lung cancer

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

Linc00342 serves as a diagnostic and prognostic biomarker in Kidney Renal Clear Cell Carcinoma:A Comprehensive Study Based on Data mining, Clinical Analysis, and in vitro Validation

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