Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells

2006 ◽  
Vol 290 (1) ◽  
pp. G129-G136 ◽  
Author(s):  
Norihisa Ishimura ◽  
Hajime Isomoto ◽  
Steven F. Bronk ◽  
Gregory J. Gores

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy; however, many cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Resistance to apoptosis may unmask TRAIL signaling cascades favoring tumor biology. Thus our aim was to examine whether TRAIL is expressed by human cholangiocarcinomas, and if so, to determine whether it promotes a malignant phenotype. To address this objective, TRAIL expression in human liver specimens was evaluated by immunohistochemistry. The effect of TRAIL on tumor cell migration, invasion, and proliferation was examined in three human cholangiocarcinoma cell lines. TRAIL expression was upregulated by cholangiocytes in preneoplastic disease, primary sclerosing cholangitis, and human cholangiocarcinoma specimens. TRAIL promoted tumor cell migration and invasion but did not induce cell proliferation. TRAIL-mediated cell migration and invasion was NF-κB dependent. These data demonstrate that TRAIL promotes cell migration and invasion via a NF-κB-dependent pathway in human cholangiocarcinoma cell lines, an observation that has a potential negative implication for TRAIL in cancer therapy.

2008 ◽  
Vol 68 (20) ◽  
pp. 8210-8220 ◽  
Author(s):  
Bharat Joshi ◽  
Scott S. Strugnell ◽  
Jacky G. Goetz ◽  
Liliana D. Kojic ◽  
Michael E. Cox ◽  
...  

2012 ◽  
Vol 287 (15) ◽  
pp. 12158-12158
Author(s):  
Hezlin Marzook ◽  
Da-Qiang Li ◽  
Vasudha S. Nair ◽  
Prakriti Mudvari ◽  
Sirigiri Divijendra Natha Reddy ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Solange Rivas ◽  
Patricio Silva ◽  
Montserrat Reyes ◽  
Hugo Sepúlveda ◽  
Luis Solano ◽  
...  

AbstractTumor hypoxia and the hypoxia inducible factor-1, HIF-1, play critical roles in cancer progression and metastasis. We previously showed that hypoxia activates the endosomal GTPase Rab5, leading to tumor cell migration and invasion, and that these events do not involve changes in Rab protein expression, suggesting the participation of intermediate activators. Here, we identified ALS2, a guanine nucleotide exchange factor that is upregulated in cancer, as responsible for increased Rab5-GTP loading, cell migration and metastasis in hypoxia. Specifically, hypoxia augmented ALS2 mRNA and protein levels, and these events involved HIF-1α-dependent transcription, as shown by RNAi, pharmacological inhibition, chromatin immunoprecipitation and bioinformatics analyses, which identified a functional HIF-1α-binding site in the proximal promoter region of ALS2. Moreover, ALS2 and Rab5 activity were elevated both in a model of endogenous HIF-1α stabilization (renal cell carcinoma) and by following expression of stable non-hydroxylatable HIF-1α. Strikingly, ALS2 upregulation in hypoxia was required for Rab5 activation, tumor cell migration and invasion, as well as experimental metastasis in C57BL/6 mice. Finally, immunohistochemical analyses in patient biopsies with renal cell carcinoma showed that elevated HIF-1α correlates with increased ALS2 expression. Hence, this study identifies ALS2 as a novel hypoxia-inducible gene associated with tumor progression and metastasis.


2016 ◽  
Vol 12 (4) ◽  
pp. 2648-2656 ◽  
Author(s):  
Meng Xu ◽  
Qingquan Liu ◽  
Yuli Jia ◽  
Kangsheng Tu ◽  
Yingmin Yao ◽  
...  

Tumor Biology ◽  
2015 ◽  
Vol 37 (5) ◽  
pp. 6831-6836 ◽  
Author(s):  
Jianting Long ◽  
Ying Xie ◽  
Junmei Yin ◽  
Wei Lu ◽  
Shi Fang

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