The prognostic value of pSTAT3 in gastric cancer: a meta-analysis

Yu, Shan; Li, G; Wang, Z; Chen, C; Cai, Shirong; He, Yulong

doi:10.1007/s00432-015-2023-1

Cited by 10 publications

(5 citation statements)

References 49 publications

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“…Activated STAT3 protein acts as a transcriptional factor to regulate cell proliferation, apoptosis, angiogenesis, tumor invasion and metastasis [35]. A metaanalysis confirmed that high expression of p-STAT3 was associated with poor prognosis of GC [36]. In addition, clinical usage of a STAT3-regulated micro-RNA signature showed a prognostic potential in early GC stratification [37].…”

Section: Discussionmentioning

confidence: 99%

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression

Yuan¹,

Ye²,

Liu

et al. 2020

J Exp Clin Cancer Res

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Background: Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. Methods: From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. Results: C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pretreated with a JAK2 inhibitor.Conclusions: Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression.

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Section: Discussionmentioning

confidence: 99%

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression

Yuan¹,

Ye²,

Liu

et al. 2020

J Exp Clin Cancer Res

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“…Activation of STAT3 transcription activity induces the expression of a wide range of target genes promoting key pro-oncogenic cellular functions, such as inflammation, proliferation, survival, invasion, and angiogenesis 28 . STAT3 is activated by phosphorylation of the Y705 position, followed by nuclear translocation of the phosphorylated proteins with subsequent activation of the transcription of specific downstream genes and metastasis of cancers 29 . Our results demonstrated decreased mRNA expression levels in GC cells featuring STAT3 knockdown and downregulation of several STAT3 target genes, such as MMP-2, MMP-14, VEGF-C, VEGF-D, and HGF.…”

Section: Discussionmentioning

confidence: 99%

RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells

Liu

Sun

et al. 2020

Cell Death Dis

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Ring finger protein 180 (RNF180) is an important member of the E3 ubiquitin ligase family. As a tumor suppressor gene, RNF180 is significantly associated with the prognosis of patients with gastric cancer (GC) and can inhibit the proliferation, invasion, and migration of GC cells. Signal transducer and activator of transcription 3 (STAT3) are considered one of the most common oncogenes in human cancers with a key role in GC progression. In this study, we explored the molecular signaling pathways by which RNF180 could potentially regulate STAT3 through transcriptomics and proteomics experiments. Here, we found RNF180 overexpression could suppress STAT3 phosphorylation in GC cells. Ubiquitin label-free experiments showed that the ubiquitination level of Ras homolog gene family member C (RhoC) is significantly increased in GC cells transfected with an RNF180 expression vector (RNF180-GFP vector) compared with cells transfected with an empty vector (vehicle vector). We subsequently demonstrated that RNF180 could directly combine with RhoC and promote the ubiquitination and degradation of RhoC protein in GC cells. The phosphorylation level of STAT3 significantly decreased in GC cells after RhoC knockdown using small hairpin RNA (shRNA). Together, these results reveal RNF180 could inhibit GC progression by reducing the phosphorylation of STAT3 via the ubiquitination and degradation of RhoC protein in GC cells. Thus, the protein may be considered a novel therapeutic target for patients with GC.

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“…A recent study on intrahepatic cholangiocarcinoma found that patients with high STAT3 expression levels had a poor overall and disease-free survival [53]. After analyzing a large number of gastric cancer cases, both STAT3 and p-STAT3 were shown to be associated with an increased mortality risk [54,55]. In another study, Deng et al reported that 62.6% (67/107) and 38% (41/107) of gastric cancer tissues exhibited positive immunostaining for STAT3 and p-STAT3, respectively [56].…”

Section: Leptin Biology and Molecules Of Relevant Signal Transductmentioning

confidence: 99%

The potential role of leptin in tumor invasion and metastasis

Ray

Cleary

2017

Cytokine & Growth Factor Reviews

110

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The adipocyte-released hormone-like cytokine/adipokine leptin behaves differently in obesity compared to its functions in the normal healthy state. In obese individuals, elevated leptin levels act as a pro-inflammatory adipokine and are associated with certain types of cancers. Further, a growing body of evidence suggests that higher circulating leptin concentrations and/or elevated expression of leptin receptors (Ob-R) in tumors may be poor prognostic factors. Although the underlying pathological mechanisms of leptin’s association with poor prognosis are not clear, leptin can impact the tumor microenvironment in several ways. For example, leptin is associated with a number of biological components that could lead to tumor cell invasion and distant metastasis. This includes interactions with carcinoma-associated fibroblasts, tumor promoting effects of infiltrating macrophages, activation of matrix metalloproteinases, transforming growth factor-β signaling, etc. Recent studies also have shown that leptin plays a role in the epithelial-mesenchymal transition, an important phenomenon for cancer cell migration and/or metastasis. Furthermore, leptin’s potentiating effects on insulin-like growth factor-I, epidermal growth factor receptor and HER2/neu have been reported. Regarding unfavorable prognosis, leptin has been shown to influence both adenocarcinomas and squamous cell carcinomas. Features of poor prognosis such as tumor invasion, lymph node involvement and distant metastasis have been recorded in several cancer types with higher levels of leptin and/or Ob-R. This review will describe the current scenario in a precise manner. In general, obesity indicates poor prognosis in cancer patients.

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The prognostic value of pSTAT3 in gastric cancer: a meta-analysis

Abstract: In conclusion, our meta-analysis suggests that positive expression of pSTAT3 is associated with poor prognosis in gastric cancer patients.

Cited by 10 publications

References 49 publications

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression

Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression

RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells

The potential role of leptin in tumor invasion and metastasis

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