C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial–mesenchymal transition

Hu, Wenhao; Hu, Zhe; Shen, Xian; Dong, Liyang; Zhou, Wei-Zhong; Yu, Xianjun

doi:10.1016/j.yexmp.2015.10.001

Cited by 50 publications

(48 citation statements)

References 24 publications

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“…Finally, we chose two EMT-related biomarkers, claudin-1 and fibronectin. Claudin-1 is considered as epithelial marker [10], and fibronectin is a mesenchymal one [11]. Upregulation of NFAT5 suppressed fibronectin expression, in the mean while induced expression of claudin-1 in hyperosmotic solution ( Figure 5A).…”

Section: Figure 2 Hyperosmolality Induces Expression Of Nfat5 (A) Rmentioning

confidence: 99%

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

Qin¹,

Wang²,

Li³

et al. 2017

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Hepatocellular carcinoma (HCC) is one of the most difficult cancer disease for diagnosis and treatment, with a low survival rate and high recurrence rate and mortality. Nuclear factor of activated T-cells 5 (NFAT5) is mediated by osmolality and proved to be a carcinogenic gene in some tumor. However in our study we considered NFAT5 as tumor suppressor of HCC. RT-qPCR was performed for NFAT5 expression in tumor tissues. NaCl was applied to make hyperosmotic treatment. We knockdowned and overexpressed NFAT5 to investigate its role in HCC. FCM was used for apoptosis assay. Transwell and scratch assay is proceeded for invasion.NFAT5 is downregulated in HCC tissue and cell lines, besides, upregulated by hyperosmolality. NFAT5 promotes apoptosis by regulating PARP-1,BAX/BCL2 while inhibits invasion through EMT-related protein claudin-1 and fibronectin. Hyperosmolality is also a protective factor for HCC. We considered hyperosmolality exhibited his protective effect by inducing NFAT5.In a word, NFAT5 inhibits invasion and promotes apoptosis in HCC, associated with osmolality.

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Section: Figure 2 Hyperosmolality Induces Expression Of Nfat5 (A) Rmentioning

confidence: 99%

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

Qin¹,

Wang²,

Li³

et al. 2017

neo

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“…Whereas gC1qR promoted angiogenesis and tumor growth, cC1qR stimulated the phagocytosis of tumor cells and was detrimental to tumor growth . Moreover, C1q was able to promote angiogenesis, as well as adhesion, proliferation, and metastasis of melanoma tumor cells independently of complement activation . The importance of other complement components in tumor biology was elegantly demonstrated by Bonavita et al., who reported that the pentraxin‐related protein PTX3 acts as an oncosuppressor regulating complement‐associated inflammation in cancer.…”

Section: Complement Activation In Cancermentioning

confidence: 99%

“…83 Moreover, C1q was able to promote angiogenesis, as well as adhesion, proliferation, and metastasis of melanoma tumor cells independently of complement activation. 84,85 The importance of other complement components in tumor biology was elegantly demonstrated by Bonavita et al, who reported that the pentraxin-related protein PTX3 acts as an oncosuppressor regulating complement-associated inflammation in cancer. PTX3 interaction with C1q and factor H downregulated complement activation, reduced local C5a accumulation within the tumor microenvironment, and hampered tumor growth.…”

Section: Tumor-promoting Activity Of Complementmentioning

confidence: 99%

“…This molecule has been shown to be essential for the initiation of complement activation in certain types of tumors and can also promote tumor growth in a complement activation independent manner. 33,85 To date, few complement-specific drugs, a monoclonal antibody to C5 and some preparations of the natural regulator C1 esterase inhibitor, have been approved by the FDA. 8 To our knowledge, none of these have been tested in cancer.…”

Section: Complement As a Therapeutic Target In Cancermentioning

confidence: 99%

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Innate immune mediators in cancer: between defense and resistance

Berraondo¹,

Minute²,

Ajona

et al. 2016

Immunological Reviews

114

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Chronic inflammation in the tumor microenvironment and evasion of the antitumor effector immune response are two of the emerging hallmarks required for oncogenesis and cancer progression. The innate immune system not only plays a critical role in perpetuating these tumor-promoting hallmarks but also in developing antitumor adaptive immune responses. Thus, understanding the dual role of the innate system in cancer immunology is required for the design of combined immunotherapy strategies able to tackle established tumors. Here, we review recent advances in the understanding of the role of cell populations and soluble components of the innate immune system in cancer, with a focus on complement, the adapter molecule Stimulator of Interferon Genes, natural killer cells, myeloid cells, and B cells.

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“…In addition, both C3a and C5a anaphylatoxins are capable of driving chemotaxis and adhesion of leukemic cells, primarily through p38 MAPK dependent downregulation of heme oxygenase 1 (Abdelbaset-Ismail et al 2016). As well as being directly chemotactic, C5aR1 has also been shown to promote epithelial to mesenchymal transition in hepatocellular carcinoma, increasing cell motility and invasiveness (Hu et al 2016).…”

Section: Migrationmentioning

confidence: 99%

Exploring the role of C5a-C5aR1 signalling in development through pluripotent stem cell modelling

Hawksworth¹

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The complement system has been traditionally described as a powerful controller of innate immunity.With activation through the recognition of pathogenic surfaces, spontaneous hydrolysis, or extrinsic cleavage, a cleavage cascade is initiated culminating in the formation of the active complement fragments C3a, C3b, C5a, and C5b. These fragments direct immune cells to sites of inflammation, as well as tagging pathogens for destruction and directly lysing foreign cells. It is now clear however, that this complex family of proteins possesses a wide range of functions outside of immune regulation. From fertilisation and morphogenesis, to the control of foetal and adult stem cell populations, studies have described novel actions of complement factors. This thesis is focussed on the central complement receptor, C5aR1. Traditionally described as a potent activating and chemotactic receptor for immune cells, C5aR1 has been shown to function in a number of nonimmune cell populations. Of note, our laboratory has previously described a role for C5aR1 in neural tube closure, with loss of C5aR1 signalling associated with increased neural tube defects under folate deficient conditions. However, a mechanistic role of C5aR1 at this stage of development was not described.In this thesis, pluripotent stem cells were utilised as an in vitro model of human development to interrogate the expression and function of C5aR1 at a number of developmental stages. Specifically, in pluripotent stem cells representative of the blastocyst inner cell mass, in neural rosettes representative of the developing ventricular zone, and in matured post-mitotic cortical neurons. This builds on previous work by our laboratory, which had identified C5aR1 actions in the mouse ventricular zone, analogous to late neural rosette cultures, and had shown a neurotoxic effect of C5aR1 in post-mitotic mouse neurons.C5aR1 was found to be expressed in pluripotent stem cells, with a role in promoting maintenance of pluripotency in the absence of FGF2 signalling. Additionally, C5aR1 was found to be apically expressed in human neural rosettes, with signalling promoting proliferation and maintenance of cell polarity. This work correlated well with mouse studies performed outside of this thesis, to show that in vivo, loss of C5aR1 in this neural progenitor population resulted in behavioural deficits and microstructural brain changes. Lastly, we determined the mRNA expression of C5aR1 in human postmitotic cortical neurons. However, in contrast to previous mouse studies, exogenous C5a, alone or in the presence of secondary stressors, had little effect on the survival of these cells.Overall, the results presented in this thesis have further expanded our knowledge of C5a-C5aR1 signalling in development, describing novel roles for this signalling pathway. The use of pluripotent stem cells allowed for the exploration of C5aR1 actions in human development that would otherwise be limited to animal models. Additionally, it allowed for the correlation of previous animal resu...

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C5a receptor enhances hepatocellular carcinoma cell invasiveness via activating ERK1/2-mediated epithelial–mesenchymal transition

Cited by 50 publications

References 24 publications

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

NFAT5 inhibits invasion and promotes apoptosis in hepatocellular carcinoma associated with osmolality

Innate immune mediators in cancer: between defense and resistance

Exploring the role of C5a-C5aR1 signalling in development through pluripotent stem cell modelling

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