scholarly journals Epigenetic Inactivation of the Canonical Wnt Antagonist SRY-Box Containing Gene 17 in Colorectal Cancer

2008 ◽  
Vol 68 (8) ◽  
pp. 2764-2772 ◽  
Author(s):  
W. Zhang ◽  
S. C. Glockner ◽  
M. Guo ◽  
E. O. Machida ◽  
D. H. Wang ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3437
Author(s):  
Hee Eun Kang ◽  
Yoojeong Seo ◽  
Jun Seop Yun ◽  
Sang Hyun Song ◽  
Dawool Han ◽  
...  

The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.


Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1331
Author(s):  
Yung-Fu Wu ◽  
Chih-Yang Wang ◽  
Wan-Chun Tang ◽  
Yu-Cheng Lee ◽  
Hoang Dang Khoa Ta ◽  
...  

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.


2013 ◽  
Author(s):  
Georg Emons ◽  
Janneke Möller ◽  
Melanie Spitzner ◽  
Emil Kendziorra ◽  
Jochen Gaedcke ◽  
...  

Oncogene ◽  
2006 ◽  
Vol 25 (29) ◽  
pp. 4116-4121 ◽  
Author(s):  
O Aguilera ◽  
M F Fraga ◽  
E Ballestar ◽  
M F Paz ◽  
M Herranz ◽  
...  

2018 ◽  
Vol 94 (1) ◽  
pp. 19 ◽  
Author(s):  
Eung Jin Shin ◽  
Han Jo Kim ◽  
Myoung Won Son ◽  
Tae Sung Ahn ◽  
Hyun Yong Lee ◽  
...  

2007 ◽  
Vol 67 (6) ◽  
pp. 2469-2479 ◽  
Author(s):  
Susmita Esufali ◽  
George S. Charames ◽  
Vaijayanti V. Pethe ◽  
Pinella Buongiorno ◽  
Bharati Bapat

2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Chunjie Xu ◽  
Guangang Tian ◽  
Chunhui Jiang ◽  
Hanbing Xue ◽  
Manzila Kuerbanjiang ◽  
...  

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