CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity

Chen, Ruo Yu; Yen, Chia Jui; Liu, Yaowen; Guo, Chun Guo; Weng, Chieh Yu; Lai, Chin‐Feng; Wang, Ju Ming; Lin, Yih Jyh; Hung, Liang‐Yi

doi:10.1038/s41418-019-0413-7

Cited by 34 publications

(28 citation statements)

References 39 publications

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“…There is increasing evidence that angiogenesis is closely related to the malignancy of liver cancer [ 23 ]. Chen found that CPAP promotes angiogenesis and metastasis in hepatocellular carcinoma [ 24 ]. In pancreatic cancer, angiogenesis is an essential factor for tumor progression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

et al. 2021

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Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA(lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of liver cancer patients, but its mechanism of action must be further elucidated by experiments.

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Section: Discussionmentioning

confidence: 99%

An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

et al. 2021

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“…Another is that targeted agents can feedback influence the activity of downstream and parallel bypass signaling pathways 40–42 . Dysregulated STAT3 signaling has been strongly implicated in tumorigenesis 43 . Nowadays studies highlight that STAT3 is activated in response to some antitumor agents, such as receptor kinase inhibitors or HDAC inhibitors 22,26 .…”

Section: Discussionmentioning

confidence: 99%

Feed‐forward activation of STAT3 signaling limits the efficacy of c‐Met inhibitors in esophageal squamous cell carcinoma (ESCC) treatment

Zhao

Chen

Wang

et al. 2021

Molecular Carcinogenesis

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c‐Hepatocyte growth factor receptor (Met) inhibitors have demonstrated clinical benefits in some types of solid tumors. However, the efficacy of c‐Met inhibitors in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we discovered that c‐Met inhibitors induced “Signal Transducer and Activator of Transcription (STAT3)‐addiction” in ESCC cells, and the feedback activation of STAT3 in ESCC cells limits the tumor response to c‐Met inhibition. Mechanistically, c‐Met inhibition increased the autocrine of several cytokines, including CCL2, interleukin 8, or leukemia inhibitory factor, and facilitated the interactions between the receptors of these cytokines and Janus Kinase1/2 (JAK1/2) to resultantly activate JAKs/STAT3 signaling. Pharmacological inhibition of c‐Met together with cytokines/JAKs/STAT3 axis enhanced cancer cells regression in vitro. Importantly, combined c‐Met and STAT3 inhibitors synergistically suppressed tumor growth and promoted the apoptosis of tumor cells without producing systematic toxicity. These findings suggest that inhibition of the STAT3 feedback loop may augment the response to c‐Met inhibitors via the STAT3‐mediated oncogene addiction in ESCC cells.

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“…As an inflammatory cytokine, IL-6 is mainly derived from stromal cells such as macrophages and fibroblasts around the tumor, and it is not secreted or is rarely secreted by the tumor cells themselves [59,60]. IL-6, similar to TNF-α, promotes the transformation of noncancer cells into cancer stem cells [61] while regulating the biological activity of tumor cells, leading to cell proliferation or distant metastasis [62]. In addition, IL-6 promotes tumor development by enhancing the T cell-mediated immuneinflammatory response, regulating gene expression, and inhibiting apoptosis in the cell through the JAK-STAT signaling pathway [63,64].…”

Section: Changes In the Tumor Inflammatory Environmentmentioning

confidence: 99%

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

Xie

Lei

et al. 2020

BioMed Research International

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Inflammatory mediators and inflammatory cells in the inflammatory microenvironment promote the transformation of normal cells to cancer cells in the early stage of cancer, promote the growth and development of cancer cells, and induce tumor immune escape. The monomeric active ingredient β-elemene is extracted from the traditional Chinese medicine Curcuma wenyujin and has been proven to have good anti-inflammatory and antitumor activities in clinical applications for more than 20 years in China. Recent studies have found that this traditional Chinese medicine plays a vital role in macrophage infiltration and M2 polarization, as well as in regulating immune disorders, and it even regulates the transcription factors NF-κB and STAT3 to alter inflammation, tumorigenesis, and development. In addition, β-elemene regulates not only different inflammatory factors (such as TNF-α, IFN, TGF-β, and IL-6/10) but also oxidative stress in vivo and in vitro. The excellent anti-inflammatory and antitumor effects of β-elemene and its ability to alter the inflammatory microenvironment of tumors have been gradually elaborated. Although the study of monomeric active ingredients in traditional Chinese medicines is insufficient in terms of quality and quantity, the pharmacological effects of more active ingredients of traditional Chinese medicines will be revealed after β-elemene.

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CPAP promotes angiogenesis and metastasis by enhancing STAT3 activity

Cited by 34 publications

References 39 publications

An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

Feed‐forward activation of STAT3 signaling limits the efficacy of c‐Met inhibitors in esophageal squamous cell carcinoma (ESCC) treatment

The Antitumor Efficacy of β-Elemene by Changing Tumor Inflammatory Environment and Tumor Microenvironment

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