ILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting β‐Catenin Degradation and Enhancing the WNT Signaling Pathway

Zhang, Rui, Yuan, Jinglei, Liu, Shicheng, Torraca, V., Liao, Zhiquan, Wu, Yueyan, Tan, Hongfei, Yao, Xia, Hou, Xueyang, Lyu, Hao, Xiao, Shuai, Guo, Dong, Ali, Declan William, Michalak, Marek, Chen, Xing‐Zhen, Zhou, C. and Tang, J. 2024. ILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting β‐Catenin Degradation and Enhancing the WNT Signaling Pathway. Advanced Biology. 8 (5) 2300117. https://doi.org/10.1002/adbi.202300117

TitleILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting β‐Catenin Degradation and Enhancing the WNT Signaling Pathway
TypeJournal article
AuthorsZhang, Rui, Yuan, Jinglei, Liu, Shicheng, Torraca, V., Liao, Zhiquan, Wu, Yueyan, Tan, Hongfei, Yao, Xia, Hou, Xueyang, Lyu, Hao, Xiao, Shuai, Guo, Dong, Ali, Declan William, Michalak, Marek, Chen, Xing‐Zhen, Zhou, C. and Tang, J.
AbstractThe incidence of Hepatocellular carcinoma (HCC) and HCC‐related deaths have remarkably increased over the recent decades. It has been reported that β‐catenin activation can be frequently observed in HCC cases. This study identified the integrin‐linked kinase‐associated phosphatase (ILKAP) as a novel β‐catenin‐interacting protein. ILKAP is localized both in the nucleus and cytoplasm and regulates the WNT pathway in different ways. First, it is demonstrated that ILKAP activates the WNT pathway in HCC cells by increasing the protein level of β‐catenin and other proteins associated with the WNT signaling, such as c‐Myc and CyclinD1. Next, it is shown that ILKAP promotes the metastasis of HCC both in vitro and in vivo in a zebrafish xenograft model. It is also found that ILKAP dephosphorylates the GSK3β and CK1, contributing to the reduced ubiquitination of β‐catenin. Furthermore, it is identified that ILKAP functions by mediating binding between TCF4 and β‐catenin to enhance expression of WNT target genes. Taken together, the study demonstrates a critical function of ILKAP in metastasis of HCC, since ILKAP is crucial for the activation of the WNT pathway via stabilization of β‐catenin and increased binding between TCF4 and β‐catenin.
Article number2300117
JournalAdvanced Biology
Journal citation8 (5)
ISSN2701-0198
Year2024
PublisherWiley
Digital Object Identifier (DOI)https://doi.org/10.1002/adbi.202300117
Publication dates
Published online20 Feb 2024
Published in printMay 2024
Project51808392
JFT 32000523
RZ 32270768 to CFZ
2022020801020272 to CFZ
2023020201020376 to RZ
2020YFC0840900
FunderNational Natural Science Foundation of China
Wuhan Science and Technology Project
National Key Research and Development Program of China

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