scholarly journals Context-Dependent Role of NF-κB Signaling in Primary Liver Cancer—from Tumor Development to Therapeutic Implications

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1053 ◽  
Author(s):  
Carolin Czauderna ◽  
Darko Castven ◽  
Friederike L. Mahn ◽  
Jens U. Marquardt

Chronic inflammatory cell death is a major risk factor for the development of diverse cancers including liver cancer. Herein, disruption of the hepatic microenvironment as well as the immune cell composition are major determinants of malignant transformation and progression in hepatocellular carcinomas (HCC). Considerable research efforts have focused on the identification of predisposing factors that promote induction of an oncogenic field effect within the inflammatory liver microenvironment. Among the most prominent factors involved in this so-called inflammation-fibrosis-cancer axis is the NF-κB pathway. The dominant role of this pathway for malignant transformation and progression in HCC is well documented. Pathway activation is significantly linked to poor prognostic traits as well as stemness characteristics, which places modulation of NF-κB signaling in the focus of therapeutic interventions. However, it is well recognized that the mechanistic importance of the pathway for HCC is highly context and cell type dependent. While constitutive pathway activation in an inflammatory etiological background can significantly promote HCC development and progression, absence of NF-κB signaling in differentiated liver cells also significantly enhances liver cancer development. Thus, therapeutic targeting of NF-κB as well as associated family members may not only exert beneficial effects but also negatively impact viability of healthy hepatocytes and/or cholangiocytes, respectively. The review presented here aims to decipher the complexity and paradoxical functions of NF-κB signaling in primary liver and non-parenchymal cells, as well as the induced molecular alterations that drive HCC development and progression with a particular focus on (immune-) therapeutic interventions.

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2184
Author(s):  
Valentina Cazzetta ◽  
Sara Franzese ◽  
Claudia Carenza ◽  
Silvia Della Bella ◽  
Joanna Mikulak ◽  
...  

Natural killer (NK) and dendritic cells (DCs) are innate immune cells that play a crucial role in anti-tumor immunity. NK cells kill tumor cells through direct cytotoxicity and cytokine secretion. DCs are needed for the activation of adaptive immune responses against tumor cells. Both NK cells and DCs are subdivided in several subsets endowed with specialized effector functions. Crosstalk between NK cells and DCs leads to the reciprocal control of their activation and polarization of immune responses. In this review, we describe the role of NK cells and DCs in liver cancer, focusing on the mechanisms involved in their reciprocal control and activation. In this context, intrahepatic NK cells and DCs present unique immunological features, due to the constant exposure to non-self-circulating antigens. These interactions might play a fundamental role in the pathology of primary liver cancer, namely hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Additionally, the implications of these immune changes are relevant from the perspective of improving the cancer immunotherapy strategies in HCC and ICC patients.


2016 ◽  
Vol 12 (1) ◽  
pp. 3-10 ◽  
Author(s):  
JIE LU ◽  
YUJING XIA ◽  
KAN CHEN ◽  
YUANYUAN ZHENG ◽  
JIANRONG WANG ◽  
...  

2019 ◽  
Vol 70 (1) ◽  
pp. e368
Author(s):  
Monika Lewinska ◽  
Deepak Kumar Bhatt ◽  
Letizia Satriano ◽  
Douglas VNP Oliveira ◽  
Friederike Mahn ◽  
...  

2017 ◽  
Vol 24 (3) ◽  
pp. 107327481772924 ◽  
Author(s):  
Ashok Shiani ◽  
Shreya Narayanan ◽  
Luis Pena ◽  
Mark Friedman

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Elisa Lozano ◽  
Elisa Herraez ◽  
Oscar Briz ◽  
Virginia S. Robledo ◽  
Jorge Hernandez-Iglesias ◽  
...  

Changes in the uptake of many drugs by the target cells may dramatically affect the pharmacological response. Thus, downregulation ofSLC22A1, which encodes the organic cation transporter type 1 (OCT1), may affect the response of healthy hepatocytes and liver cancer cells to cationic drugs, such as metformin and sorafenib, respectively. Moreover, the overall picture may be modified to a considerable extent by the preexistence or the appearance during the pathogenic process of genetic variants. Some rare OCT1 variants enhance transport activity, whereas other more frequent variants impair protein maturation, plasma membrane targeting or the function of this carrier, hence reducing intracellular active drug concentrations. Here, we review current knowledge of the role of OCT1 in modern liver pharmacology, which includes the use of cationic drugs to treat several diseases, some of them of great clinical relevance such as diabetes and primary liver cancer (cholangiocarcinoma and hepatocellular carcinoma). We conclude that modern pharmacology must consider the individual evaluation of OCT1 expression/function in the healthy liver and in the target tissue, particularly if this is a tumor, in order to predict the lack of response to cationic drugs and to be able to design individualized pharmacological treatments with the highest chances of success.


1986 ◽  
Vol 2 (2) ◽  
pp. 103-112 ◽  
Author(s):  
Zhao-You Tang ◽  
Ye-Qin Yu ◽  
Xin-Da Zhou

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