Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex

大黄酚通过靶向 KITENIN/ErbB4 致癌复合物抑制结直肠癌细胞迁移和能量代谢

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作者:Mücahit Varlı, Eunae Kim, Songjin Oh, Sultan Pulat, Rui Zhou, Chathurika D B Gamage, Barış Gökalsın, Nüzhet Cenk Sesal, Kyung Keun Kim, Man-Jeong Paik, Hangun Kim

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.

Conclusion

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.

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