Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

Zhang, Mingdi; Gong, Wei; Zhang, Yong; Yang, Yong; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Jiang, Alex; Ma, Fei; Quan, Zhiwei

doi:10.3892/mmr.2014.3143

Cited by 19 publications

(19 citation statements)

References 32 publications

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“…Moreover, IL-6 promotes the migration and invasion of multiple tumor cells, via the induction of EMT [39]. For example, the overexpression of IL-6 enhances the invasion and migration of gallbladder cancer cells, by stimulating EMT [40]. In this study, we found that exogenous IL-6 induced a significant downregulation of E-cadherin, and an enhancement of migration in the breast cancer cell line T47D.…”

Section: Discussionmentioning

confidence: 57%

Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

Sun

Zhang

Wang

et al. 2017

IJMS

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Accumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors. However, whether Shp2 is involved in IL-6-signaling-promoted breast cancer EMT and progression, remains undefined. In this study, we showed that exogenous and endogenous IL-6 can enhance breast cancer invasion and migration, through the promotion of EMT. IL-6 also induces the activation of Erk1/2 and the phosphorylation of Shp2. Knockdown of Shp2 attenuated the IL-6-induced downregulation of E-cadherin, as well as IL-6-promoted cell migration and invasion. Moreover, by using Shp2 phosphatase mutants, phosphor-tyrosine mimicking, and deficiency mutants, we provided evidence that the phosphatase activity of Shp2 and its tyrosine phosphorylation, are necessary for the IL-6-induced downregulation of E-cadherin and the phosphorylation of Erk1/2. Our findings uncover an important function that links Shp2 to IL-6-promoted breast cancer progression.

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Section: Discussionmentioning

confidence: 57%

Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

Sun

Zhang

Wang

et al. 2017

IJMS

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“…IL-6 is also a multi-functional cytokine secreted by a variety of cell types and is frequently involved in a series of physiological and pathological effects, including inflammation and fibrosis (30). Aberrant expression of IL-6 is associated with the poor prognosis of patients with glioma (31), and gallbladder and colon cancer types (32,33). The effects of p53 wt on the release of autocrine cytokines IL-10 and IL-6 and their protein expression levels in NCI-H1299 cells were also investigated in the present study, which indicated that p53 inhibits IL-10 in vitro autocrine and protein expression, but does not exert any influence on IL-6.…”

Section: Discussionmentioning

confidence: 99%

Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein�18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells

et al. 2019

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Our previous studies demonstrated that high expression of oncoprotein 18 (Op18)/stathmin promotes malignant transformation of non-small cell lung cancer NCI-H1299 cells. Investigation of the cellular settings determined that NCI-H1299 cells were genetically p53 deficient. In order to determine whether p53 deficiency is associated with Op18/stathmin-mediated high levels of malignancy, exogenous wild-type p53 (p53 wt) was introduced into NCI-H1299 cells in the present study to observe Op18/stathmin signaling changes and malignant behaviors. The results indicated that p53 downregulated Op18/stathmin expression and phosphorylation at the Ser25 and Ser63 sites in NCI-H1299 cells, and the abilities of proliferation, colony formation and migration in multi-dimensional spaces were simultaneously reduced. Introduction of p53 wt inhibited the expression of the transcription factor nuclear factor-κB (NF-κB), and the activities of the Op18/stathmin upstream kinases cyclin-dependent 2 (CDC2) and extracellular signal-regulated kinase (ERK). Furthermore, blocking of NF-κB signaling decreased CDC2 and ERK activation. Additionally, p53 intervention attenuated the secretion and protein expression of the immune inhibitory cytokine interleukin-10, which was in accordance with the effect of NF-κB signaling inhibition. Further experiments validated that p53 enhanced the sensitivity of NCI-H1299 cells to Taxol through initiating the caspase-3 and-9 intrinsic death pathways, and resulted in cell cycle arrest at the G 1 /S phases. These data indicated that exogenous p53 wt mediates the regulation of Op18/stathmin signaling through the p53-NF-κB-CDC2/ERK-Op18/stathmin pathway, and that p53 deficiency is associated with high malignancy levels of NCI-H1299 cells.

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“…Furthermore, it is difficult to identify the underlying mechanisms through which IL-6/IL-6R signalling regulate the carcinogenesis, progression and metastasis of ccRCC. An immunosuppressive effect on dendritic cells, a proinflammatory role through trans-signalling pathway, a growth factor effect and an epithelial–mesenchymal transition promoter role could all contribute to these observations; there are many works to accomplish before fully understanding the roles of IL-6 in RCC ( Cabillic et al , 2006 ; Jones et al , 2011 ; Wolf et al , 2014 ; Zhang et al , 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis

Chang

et al. 2015

Br J Cancer

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Background:Interleukin-6 (IL-6) is the major cytokine that induces transcriptional acute and chronic inflammation responses, and was recently incorporated as a recurrence prognostication signature for localised clear-cell renal cell carcinoma (ccRCC). As the prognostic efficacy of initial risk factors may ebb during long-term practice, we aim to report conditional cancer-specific survival (CCSS) of RCC patients and evaluate the impact of IL-6 as well as its receptor (IL-6R) to offer more relevant prognostic information accounting for elapsing time.Methods:We enrolled 180 histologically proven localised ccRCC patients who underwent nephrectomy between 2001 and 2004 with available pathologic information. Five-year CCSS was determined and stratified by future prognostic factors. Constant Cox regression analysis and Harrell's concordance index were used to indicate the predictive accuracy of established models.Results:The 5-year CCSS of organ-confined ccRCC patients with both IL-6- and IL-6R-positive expression was 52% at year 2 after surgery, which was close to locally advanced patients (48%, P=0.564) and was significantly poorer than organ-confined patients with IL-6- or IL-6R-negative expression (89%, P<0.001). Multivariate analyses proved IL-6 and IL-6R as independent predictors after adjusting for demographic factors. Concordance index of pT-IL-6-IL-6R risk stratification was markedly higher compared with the stage, size, grade and necrosis prognostic model (0.724 vs 0.669, P=0.002) or UCLA Integrated Staging System (0.724 vs 0.642, P=0.007) in organ-confined ccRCC population during the first 5 years.Conclusions:Combined IL-6 and IL-6R coexpression emerges as an independent early-stage immunologic prognostic factor for organ-confined ccRCC patients.

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Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

Cited by 19 publications

References 32 publications

Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells

Introduction of exogenous wild‑type p53 mediates the regulation of oncoprotein�18/stathmin signaling via nuclear factor‑κB in non‑small cell lung cancer NCI‑H1299 cells

Prognostic value of interleukin-6 and interleukin-6 receptor in organ-confined clear-cell renal cell carcinoma: a 5-year conditional cancer-specific survival analysis

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