ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness
Abstract Rho GTPase-activating protein 4 (ARHGAP4) is implicated in poor prognosis across multiple malignancies. However, its role in driving stemness in colorectal cancer (CRC) remains unclear. In this study, we demonstrate that ARHGAP4 drives CRC stemness through a positive feedback loop involving...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-01022-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849238017129054208 |
|---|---|
| author | Shaolin Liu Yizhen Chen Song Tan Yifan Chen Changshun Yang Yulong Mi Shengtao Lin Weihua Li |
| author_facet | Shaolin Liu Yizhen Chen Song Tan Yifan Chen Changshun Yang Yulong Mi Shengtao Lin Weihua Li |
| author_sort | Shaolin Liu |
| collection | DOAJ |
| description | Abstract Rho GTPase-activating protein 4 (ARHGAP4) is implicated in poor prognosis across multiple malignancies. However, its role in driving stemness in colorectal cancer (CRC) remains unclear. In this study, we demonstrate that ARHGAP4 drives CRC stemness through a positive feedback loop involving MYH9/β-catenin/c-Jun, as validated by integrated bioinformatics analysis, in vitro and in vivo tumor stemness assays, co-immunoprecipitation, chromatin immunoprecipitation, and fluorescence recovery after photobleaching. These findings identify ARHGAP4 as a promising therapeutic target in CRC, particularly for addressing cancer stem cells (CSCs). |
| format | Article |
| id | doaj-art-bc761822473e4bbd84841ce262cacac3 |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-bc761822473e4bbd84841ce262cacac32025-08-20T04:01:47ZengNature Portfolionpj Precision Oncology2397-768X2025-08-019111710.1038/s41698-025-01022-4ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemnessShaolin Liu0Yizhen Chen1Song Tan2Yifan Chen3Changshun Yang4Yulong Mi5Shengtao Lin6Weihua Li7Shengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityShengli Clinical Medical College of Fujian Medical UniversityDepartment of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalDepartment of Gastrointestinal Surgery, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial HospitalAbstract Rho GTPase-activating protein 4 (ARHGAP4) is implicated in poor prognosis across multiple malignancies. However, its role in driving stemness in colorectal cancer (CRC) remains unclear. In this study, we demonstrate that ARHGAP4 drives CRC stemness through a positive feedback loop involving MYH9/β-catenin/c-Jun, as validated by integrated bioinformatics analysis, in vitro and in vivo tumor stemness assays, co-immunoprecipitation, chromatin immunoprecipitation, and fluorescence recovery after photobleaching. These findings identify ARHGAP4 as a promising therapeutic target in CRC, particularly for addressing cancer stem cells (CSCs).https://doi.org/10.1038/s41698-025-01022-4 |
| spellingShingle | Shaolin Liu Yizhen Chen Song Tan Yifan Chen Changshun Yang Yulong Mi Shengtao Lin Weihua Li ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness npj Precision Oncology |
| title | ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness |
| title_full | ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness |
| title_fullStr | ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness |
| title_full_unstemmed | ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness |
| title_short | ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness |
| title_sort | arhgap4 myh9 β catenin c jun positive feedback loop promotes colorectal cancer stemness |
| url | https://doi.org/10.1038/s41698-025-01022-4 |
| work_keys_str_mv | AT shaolinliu arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT yizhenchen arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT songtan arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT yifanchen arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT changshunyang arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT yulongmi arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT shengtaolin arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness AT weihuali arhgap4myh9bcatenincjunpositivefeedbacklooppromotescolorectalcancerstemness |