The JAK/STAT signaling cascade in gastric carcinoma (Review)

Khanna, Puja; Chua, Pei Jou; Bay, Boon Huat; Baeg, Gyeong Hun

doi:10.3892/ijo.2015.3160

Cited by 70 publications

(57 citation statements)

References 125 publications

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“…24 Interestingly, our results also showed that PODXL was expressed more frequently in GC tis- Recent studies on the genomic landscape of gastric adenocarcinoma have identified several key signaling molecules, including epidermal growth factor receptor family (ErbB) members, vascular endothelial growth factor (VEGFR) receptor family members, and PI3K/Akt, NF-κB and MAPK/ERK pathway components, that were implicated in the molecular pathogenesis of GC. 37 For example, PI3Kp85α and p-AKT were expressed in gastric adenocarcinoma tissues, and targeting blockade of the PI3K pathway might inhibit GC growth and metastasis through downregulation of Ki-67 and MMP-2 expression. 38 Consistent with these findings, the PI3K/Akt inhibitor LY294002 effectively enhanced the chemosensitivity of human GC cells to vincristine.…”

Section: Discussionmentioning

confidence: 99%

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

et al. 2018

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Podocalyxin‐like protein (PODXL), a transmembrane glycoprotein with anti‐adhesive properties, is associated with an aggressive tumor phenotype and poor prognosis of several cancers. To elucidate the biological significance of PODXL and its molecular mechanism in gastric cancer (GC), we investigated the expression of PODXL in GC samples and assessed its effects on biological behaviors and the related signaling pathways in vitro and in vivo. Moreover, the possible and closely interacted partners of PODXL were identified. Our data showed that the protein or mRNA level of PODXL was significantly upregulated in tissues or serum of GC patients compared with normal‐appearing tissues (NAT) or those of healthy volunteers. Overall survival (OS) curves showed that patients with high PODXL levels in tissues or serum had a worse 5‐year OS. In vitro, restoring PODXL expression promoted tumor progression by increasing cell proliferation, colony formation, wound healing, migration and invasion, as well as suppressing the apoptosis. Furthermore, the PI3K/AKT, NF‐κB and MAPK/ERK signaling pathways were activated. There was a significant positive correlation between PODXL and RUN and FYVE domain containing 1 (RUFY1) expression in tissues or serum. Subsequent mass spectrometry analysis, co‐immunoprecipitation assays and western blot analysis identified PODXL/RUFY1 complexes in GC cells, and silencing RUFY1 expression in GC cells significantly attenuated PODXL‐induced phenotypes and their underlying signaling pathways. Our results suggested that PODXL promoted GC progression via a RUFY1‐dependent signaling mechanism. New GC therapeutic opportunities through PODXL and targeting the PODXL/RUFY1 complex might improve cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

et al. 2018

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“…It is known that the PI3K/AKT/mTOR signaling pathway is frequently activated in GC and plays a crucial role in mediating multiple cellular functions including cell proliferation, metastasis, and resistance to chemotherapy [23,[35][36][37][38]. PI3K/AKT/mTOR acted as an important pathway to regulate the progression of GC [39][40][41][42]. The Western blot and IHC staining farther con rmed that WTX negatively regulated PI3K/AKT/mTOR pathway activity and inhibited GC proliferation.…”

Section: Discussionmentioning

confidence: 97%

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

Shen

et al. 2020

Preprint

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Background: The X-linked gene WTX (also called AMER1), has been reported to act as a tumor suppress gene in Wilms tumor. Our previous study reported that WTX expression was significantly reduced in gastric cancer (GC), but the function and mechanism of WTX loss had not been fully elucidated yet. Methods: WTX/miR-20a-5p expression was analyzed in paraffin-embedded archived GC tissues and validated in public databases. KEGG pathway analyses were performed to explore the mechanism of WTX in GC progression. The role of WTX/miR-20a-5p in cell growth, migration, invasion and angiogenesis was investigated in vitro and in vivo. Western blot, immunohistochemistry, RT-PCR, luciferase assay, and Co-immunoprecipitation (Co-IP) were used to detect the regulation of WTX and PI3K/AKT/mTOR signaling by miR-20a-5p.Results: We revealed that WTX served as a tumor suppressor whose loss associated with the aggressive feature of GC by showing hyperproliferation in vitro and high metastasis phenotype in vivo. And WTX expression level was positively correlated with the overall survival of GC patients. Microarray, bioinformatics analysis, and verification experiments showed that WTX loss activated PI3K/AKT/mTOR pathway, and promoted the proliferation and invasion of GC cells. We also discovered that the miR-20a-5P aberrant upregulation was one of the reasons inducing WTX loss in GC which stimulated PI3K phosphorylation to activate PI3K/AKT/mTOR signaling pathway, thus promoted GC progression.Conclusions: This study unveiled the mechanism of GC progression which was, at least partially, caused by miR-20a-5p aberrant upregulation which inhibited WTX expression and thus activate PI3K/AKT/mTOR signaling pathway. It provided a comprehensive understanding of the action of miR-20a-5p/WTX/PI3K/AKT/mTOR signaling pathway in the progression and metastasis of GC.

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“…Besides the well-known signaling pathways that FOXM1 and PLAU involved in, our results also indicate that FOXM1 and PLAU may participate in the JAK-STAT3, DNA repair and drug resistance (Docetaxel and Doxorubicin) in GC. JAK2-STAT3 axis activation is the feature in many solid tumor and play an important role in cell proliferation and microenvironment changed [56,57]. Drugs targeting on JAK2-STAT3 pathway in autoimmune disease have been shown in phase 3 trial, but no response was seen in solid tumor even in the phase 1 trial [58,59].…”

Section: Discussionmentioning

confidence: 99%

FOXM1 functions collaboratively with PLAU to promote gastric cancer progression

Ai¹,

Zhang²,

Lian³

et al. 2020

J. Cancer

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Background: Gastric cancer (GC) is one of the main mortality cause worldwide. Previously, we found Forkhead box protein (FOXM1) or Urokinase-type plasminogen activator (PLAU) are independent prognostic markers of GC. This study aims to explore the combining prognostic efficacy and the potential insights underlying additive effect of FOXM1 to PLAU in GC progression through in-silico analyses. Method: The expression of FOXM1 and PLAU were profiled in 33 cancer types using public data. A merged GC expression dataset containing 598 samples was used for evaluating prognostic significance of FOXM1/PLAU. Gene Set Enrichment Analysis (GSEA) was performed to elucidate the mechanisms underlying FOXM1/PLAU promoted GC progression. The Cancer Genome Atlas (TCGA) was used for analyzing the association between FOXM1/PLAU and tumor immune infiltration. Genomic and proteomic differences between FOXM1+PLAU+ and FOXM1-PLAU-groups were also computed using TCGA GC data. Drugs targeting FOXM1/PLAU associated gene expression pattern was analyzed using LINCs database. Results: FOXM1 and PLAU are overexpressed in 17/33 cancer types including GC. Kaplan-Meier analyses indicate that the FOXM1+PLAU+ subgroup have the worst prognosis, while FOXM1-PLAU-subgroup have the best survival. Bioinformatics analysis indicated that FOXM1+PLAU+ associated genes are enriched in TGF-beta, DNA repair and drug resistance signaling pathways; FOXM1 and PLAU expression are negatively correlated with tumor immune infiltration. Genomic and proteomic differences between FOXM1+PLAU+ and FOXM1-PLAU-groups were presented. Data mining from LINCs suggested several chemicals or drugs that could target the gene expression pattern of FOXM1+PLAU+ patients. Conclusion: FOXM1+PLAU+ can serve as effective prognostic biomarkers and potential therapeutic targets for GC. Due to the additive effect of these two genes, screening for drugs or chemicals that targeting the expression patterns PLAU+FOXM1+ subgroup may exert important clinical impact on GC management.

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The JAK/STAT signaling cascade in gastric carcinoma (Review)

Cited by 70 publications

References 125 publications

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

Podocalyxin‐like protein promotes gastric cancer progression through interacting with RUN and FYVE domain containing 1 protein

Mir-20a-5p Induced WTX Deficiency Promotes Gastric Cancer Progressions Through Regulating PI3K/AKT Signaling Pathway

FOXM1 functions collaboratively with PLAU to promote gastric cancer progression

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