PDF(Pubmed)
Abstract：
BACKGROUND: Expression of the KITENIN/ErbB4 oncogenic complex is associated with metastasis of colorectal cancer to distant organs and lymph nodes and is linked with poor prognosis and poor survival.
METHODS: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex.
RESULTS: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites.
CONCLUSIONS: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.
METHODS: Here, we used in vitro and in silico methods to test the ability of chrysophanol, a molecule of natural origin, to suppress the progression of colorectal cancer by targeting the KITENIN/ErbB4 complex.
RESULTS: Chrysophanol binds to ErbB4, disrupting the ErbB4/KITENIN complex and causing autophagic degradation of KITENIN. We demonstrated that chrysophanol binds to ErbB4 according to a molecular docking model. Chrysophanol reversed KITENIN-mediated effects on cell motility, aerobic glycolysis, and expression of downstream effector genes. Moreover, under conditions of KITENIN overexpression, chrysophanol suppressed the production of onco-metabolites.
CONCLUSIONS: Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.
摘要：
背景：KITENIN/ErbB4致癌复合物的表达与结直肠癌向远处器官和淋巴结的转移有关，并与不良预后和不良生存率有关。
方法：这里，我们使用体外和计算机模拟方法来测试大黄酚的能力，一种天然来源的分子，通过靶向KITENIN/ErbB4复合物抑制结直肠癌的进展。
结果：大黄酚与ErbB4结合，破坏ErbB4/KITENIN复合物并引起KITENIN的自噬降解。根据分子对接模型，我们证明了大黄酚与ErbB4结合。大黄酚逆转KITENIN介导的细胞运动效应，有氧糖酵解，和下游效应基因的表达。此外，在KITENIN过表达的条件下，大黄酚抑制癌代谢物的产生。
结论：大黄酚通过靶向KITENIN/ErbB4复合物抑制致癌活性。
方法：这里，我们使用体外和计算机模拟方法来测试大黄酚的能力，一种天然来源的分子，通过靶向KITENIN/ErbB4复合物抑制结直肠癌的进展。
结果：大黄酚与ErbB4结合，破坏ErbB4/KITENIN复合物并引起KITENIN的自噬降解。根据分子对接模型，我们证明了大黄酚与ErbB4结合。大黄酚逆转KITENIN介导的细胞运动效应，有氧糖酵解，和下游效应基因的表达。此外，在KITENIN过表达的条件下，大黄酚抑制癌代谢物的产生。
结论：大黄酚通过靶向KITENIN/ErbB4复合物抑制致癌活性。
