scholarly journals A positive feedback loop of p53/miR-19/TP53INP1 modulates pancreatic cancer cell proliferation and apoptosis

2015 ◽  
Vol 35 (1) ◽  
pp. 518-523 ◽  
Author(s):  
XIAOFANG WANG ◽  
LEI WANG ◽  
QINGJIANG MO ◽  
ANKUI JIA ◽  
YUQIAN DONG ◽  
...  
Oncogene ◽  
2021 ◽  
Author(s):  
Hirokazu Kimura ◽  
Ryota Sada ◽  
Naoki Takada ◽  
Akikazu Harada ◽  
Yuichiro Doki ◽  
...  

AbstractDickkopf1 (DKK1) is overexpressed in various cancers and promotes cancer cell proliferation by binding to cytoskeleton-associated protein 4 (CKAP4). However, the mechanisms underlying DKK1 expression are poorly understood. RNA sequence analysis revealed that expression of the transcription factor forkhead box M1 (FOXM1) and its target genes concordantly fluctuated with expression of DKK1 in pancreatic ductal adenocarcinoma (PDAC) cells. DKK1 knockdown decreased FOXM1 expression and vice versa in PDAC and esophageal squamous cell carcinoma (ESCC) cells. Inhibition of either the DKK1-CKAP4-AKT pathway or the ERK pathway suppressed FOXM1 expression, and simultaneous inhibition of both pathways showed synergistic effects. A FOXM1 binding site was identified in the 5ʹ-untranslated region of the DKK1 gene, and its depletion decreased DKK1 expression and cancer cell proliferation. Clinicopathological and database analysis revealed that PDAC and ESCC patients who simultaneously express DKK1 and FOXM1 have a poorer prognosis. Multivariate analysis demonstrated that expression of both DKK1 and FOXM1 is the independent prognostic factor in ESCC patients. Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.


2021 ◽  
Vol Volume 14 ◽  
pp. 145-155
Author(s):  
Jianjun Wang ◽  
Yuchen Li ◽  
Binbin Xu ◽  
Jiao Dong ◽  
Haiyan Zhao ◽  
...  

2019 ◽  
Vol 71 (2) ◽  
pp. 301-311 ◽  
Author(s):  
Susan S. C. Cheung ◽  
David Hasman ◽  
Djamel Khelifi ◽  
Joseph Tai ◽  
Richard W. Smith ◽  
...  

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