Dysregulation of Wnt/β-catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.

Qian Li, Mengqing Sun, Menglan Wang, Mengqing Feng, Fan Yang, Lina Li, Jianbo Zhao, Cunjie Chang, Heng Dong, Tian Xie, Jianxiang Chen

Journal: Cancer science 2021;112(5):1695-1706

PMID: 33605517

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Abstract

Wnt/β-catenin signaling is indispensable for many biological processes, including embryonic development, cell cycle, inflammation, and carcinogenesis. Aberrant activation of the Wnt/β-catenin signaling can promote tumorigenicity and enhance metastatic potential in hepatocellular carcinoma (HCC). Targeting this pathway is a new opportunity for precise medicine for HCC. However, inhibiting Wnt/β-catenin signaling alone is unlikely to significantly improve HCC patient outcome due to the lack of specific inhibitors and the complexity of this pathway. Combination with other therapies will be an important next step in improving the efficacy of Wnt/β-catenin signaling inhibitors. Protein kinases play a key and evolutionarily conserved role in the Wnt/β-catenin signaling and have become one of the most important drug targets in cancer. Targeting Wnt/β-catenin signaling and its regulatory kinase together will be a promising HCC management strategy. In this review, we summarize the kinases that modulate the Wnt/β-catenin signaling in HCC and briefly discuss their molecular mechanisms. Furthermore, we list some small molecules that target the kinases and may inhibit Wnt/β-catenin signaling, to offer new perspectives for preclinical and clinical HCC studies.

Address: Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Department of Hepatology, Institute of Hepatology and Metabolic Diseases, Institute of Integrated Chinese and Western Medicine for Oncology, The Affiliated Hospital of Hangzhou Normal University, College of Pharmacy, School of Medicine, Hangzhou Normal University, Hangzhou, China.; Division of Cellular and Molecular Research, Laboratory of Cancer Genomics, National Cancer Centre, Singapore City, Singapore.

DOI: 10.1111/cas.14861