&lt;p&gt;CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling&lt;/p&gt;

Shao, Qingliang; Zhang, Zhiqiang; Cao, Rongxian; Zang, Hui; Pei, Wanting; Sun, Tian

doi:10.2147/ott.s257057

Cited by 29 publications

(13 citation statements)

References 45 publications

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“…In the development of ovarian cancer, several signaling pathways are aberrantly activated, including the PI3K/AKT signaling pathway, MEK/ERK signaling pathway, and Wnt/β-catenin signaling pathway, which are also coincidentally closely related to the EMT process ( Dongre and Weinberg, 2019 ). Among them, the PI3K/AKT signaling pathway is the most frequently activated pathway ( Ediriweera et al, 2019 ; Zhang et al, 2019 ; Nguyen et al, 2019 ), which is also involved in regulating cell proliferation, apoptosis, invasion, survival, and angiogenesis ( Shao et al, 2020 ). Liu et al (2020) used GeneCards and OMIM databases for the enrichment analysis and found that CA is closely related to the AKT/PI3K signaling pathway in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

Wang

et al. 2022

Front. Pharmacol.

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Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. In vivo, we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that in vitro CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in in vivo, CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis in vivo and in vitro and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

Wang

et al. 2022

Front. Pharmacol.

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“…Several MCPs have been linked to chronic human diseases, such as cancer, fibrinolysis, and inflammation, as well as infectious diseases. Consequently, MCPs and their inhibitors have attracted considerable medical interest as potential drug targets [ 2 , 3 , 32 , 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of NpCI, a New Metallocarboxypeptidase Inhibitor from the Marine Snail Nerita peloronta with Anti-Plasmodium falciparum Activity

et al. 2023

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Metallocarboxypeptidases are zinc-dependent peptide-hydrolysing enzymes involved in several important physiological and pathological processes. They have been a target of growing interest in the search for natural or synthetic compound binders with biomedical and drug discovery purposes, i.e., with potential as antimicrobials or antiparasitics. Given that marine resources are an extraordinary source of bioactive molecules, we screened marine invertebrates for new inhibitory compounds with such capabilities. In this work, we report the isolation and molecular and functional characterization of NpCI, a novel strong metallocarboxypeptidase inhibitor from the marine snail Nerita peloronta. NpCI was purified until homogeneity using a combination of affinity chromatography and RP-HPLC. It appeared as a 5921.557 Da protein with 53 residues and six disulphide-linked cysteines, displaying a high sequence similarity with NvCI, a carboxypeptidase inhibitor isolated from Nerita versicolor, a mollusc of the same genus. The purified inhibitor was determined to be a slow- and tight-binding inhibitor of bovine CPA (Ki = 1.1·× 10−8 mol/L) and porcine CPB (Ki = 8.15·× 10−8 mol/L) and was not able to inhibit proteases from other mechanistic classes. Importantly, this inhibitor showed antiplasmodial activity against Plasmodium falciparum in an in vitro culture (IC50 = 5.5 μmol/L), reducing parasitaemia mainly by inhibiting the later stages of the parasite’s intraerythrocytic cycle whilst having no cytotoxic effects on human fibroblasts. Interestingly, initial attempts with other related proteinaceous carboxypeptidase inhibitors also displayed similar antiplasmodial effects. Coincidentally, in recent years, a metallocarboxypeptidase named PfNna1, which is expressed in the schizont phase during the late intraerythrocytic stage of the parasite’s life cycle, has been described. Given that NpCI showed a specific parasiticidal effect on P. falciparum, eliciting pyknotic/dead parasites, our results suggest that this and related inhibitors could be promising starting agents or lead compounds for antimalarial drug discovery strategies.

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“…It was noted that CPA4 levels are elevated in diverse malignancies, including non‐small cell lung, liver, breast, prostate and colorectal cancers 57–61 . Shao et al 62 noted that the activation of the PI3K/Akt/mammalian target of rapamycin signaling pathway through CPA4 enhanced the epithelial–mesenchymal transition in pancreatic cancer. Moreover, several studies have explored the roles associated with the eight genes involved in the gene signature of CC.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive study of oxidative stress‐related effects on the prognosis and drug therapy of cervical cancer

Sheng,

He,

Jin

et al. 2023

The Journal of Gene Medicine

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BackgroundCervical cancer (CC) is a serious global disease with poor prognoses and a significant recurrence rate in patients with advanced disease. Oxidative stress (OS) greatly influences many types of human cancers, making it crucial to understand the functional mechanisms of OS‐related genes in CC.MethodsThe transcriptome and clinical data of three normal samples and 306 patients with CC were obtained from The Cancer Genome Atlas dataset. The GSE44001 dataset was acquired from the Gene Expression Omnibus database. OS‐related subtypes in the cohort with CC were identified using unsupervised hierarchical clustering, univariate Cox analysis, gene set enrichment analysis (GSEA), and least absolute shrinkage and selection operator regression analysis. Additionally, molecular pathways that differ across subtypes were determined and OS‐related genes linked to the prognosis of patients of CC were determined. Finally, a clinical prognostic gene signature was developed and validated. The relative infiltration level of immune cell subpopulations in different risk groups and subtypes was evaluated using the cell‐type identification by estimating relative subsets of RNA transcripts (CIBERPORT) algorithm and single‐sample GSEA (ssGSEA) techniques.ResultsThe present study established two distinct OS subtypes (OS clusters A and B). Analysis using ssGSEA and CIBERSPORT revealed that OS cluster B exhibited a significant level of immune infiltration. A clinical prognostic gene signature was established using OS‐related characteristic genes identified by examining the differentially expressed genes across both subtypes. Furthermore, patients with CC were grouped into high‐ and low‐risk groups, with the low‐risk group showing higher survival rates. Additionally, these individuals exhibited significant advantages in terms of survival and immunotherapy. Receiver operating characteristic curve analysis demonstrated the higher predictive value of the clinical prognostic gene signature. The outcomes of the validation group depicted congruence with those recorded in the training group.ConclusionsA new model was constructed based on eight OS‐related characteristic genes to aid the prediction of the survival rates of individuals with CC. The present study contributes to the existing literature on the mechanisms of OS genes in CC and offers a fresh perspective for future advancements in immunotherapy for such individuals.

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<p>CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling</p>

Cited by 29 publications

References 45 publications

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

Isolation and Characterization of NpCI, a New Metallocarboxypeptidase Inhibitor from the Marine Snail Nerita peloronta with Anti-Plasmodium falciparum Activity

A comprehensive study of oxidative stress‐related effects on the prognosis and drug therapy of cervical cancer

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