biostudies-literatureVarlı MScientific and Technological Research Council of TürkiyeNational Research Foundation of Korea253https://www.ebi.ac.uk/biostudies/studies/S-EPMC11264950biostudies-literatureUnknown24(1)<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.Cancer cell internationalChrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.PMC11264950RS-2023-00250803218S752Varlı MPulat SGokalsın BKim KKSesal NCKim HKim EZhou RGamage CDBOh SPaik MJfalseChrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>Chrysophanol suppresses oncogenic activities by targeting the KITENIN/ErbB4 complex.2024-01-01T00:00:00Z2024 Jul2026-06-02T09:08:59.761Z2025-06-01T01:17:00.552ZS-EPMC112649503903059410.1186/s12935-024-03434-x