Dysregulation of Wnt/β-catenin signaling by protein kinases in hepatocellular carcinoma and its therapeutic application.
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.
['Li|Qian|Q|https://orcid.org/0000-0002-2560-5730', 'Sun|Mengqing|M|', 'Wang|Menglan|M|', 'Feng|Mengqing|M|', 'Yang|Fan|F|', 'Li|Lina|L|', 'Zhao|Jianbo|J|', 'Chang|Cunjie|C|', 'Dong|Heng|H|', 'Xie|Tian|T|', 'Chen|Jianxiang|J|']
D060465:Axin Signaling Complex D016203:CDC2 Protein Kinase D006528:Carcinoma, Hepatocellular D003131:Combined Modality Therapy D003402:Creatine Kinase D018844:Cyclin-Dependent Kinases D066246:ErbB Receptors D051417:Focal Adhesion Kinase 1 D000071679:Glycogen Synthase Kinase 3 beta D006801:Humans D008113:Liver Neoplasms D060492:Low Density Lipoprotein Receptor-Related Protein-5 D060488:Low Density Lipoprotein Receptor-Related Protein-6 D020930:MAP Kinase Kinase Kinases D000072379:NIMA-Related Kinases D057285:Precision Medicine D047428:Protein Kinase Inhibitors D011494:Protein Kinases D017346:Protein Serine-Threonine Kinases D019859:Proto-Oncogene Proteins c-met D020794:Receptor Protein-Tyrosine Kinases D057050:Receptor Tyrosine Kinase-like Orphan Receptors D051153:Wnt Proteins D060449:Wnt Signaling Pathway D051176:beta Catenin D054462:p21-Activated Kinases D019061:src-Family Kinases
Wnt β-catenin signaling protein kinase hepatocellular carcinoma small molecule combination therapy