The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression
Recurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been dem...
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2021-12-01
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| author | Jang-Hyun Choi Tae-Young Jang So-El Jeon Jee-Heun Kim Choong-Jae Lee Hyeon-Ji Yun Ji-Youn Jung So-Yeon Park Jeong-Seok Nam |
| author_facet | Jang-Hyun Choi Tae-Young Jang So-El Jeon Jee-Heun Kim Choong-Jae Lee Hyeon-Ji Yun Ji-Youn Jung So-Yeon Park Jeong-Seok Nam |
| author_sort | Jang-Hyun Choi |
| collection | DOAJ |
| description | Recurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been demonstrated to be more effective than existing chemotherapeutic drugs, resulting in a significant unmet need for effective CRC therapies. In this study, transcriptomic profiling of metastatic tumors from CRC patients revealed significant upregulation in the Wnt pathway and stemness genes. Thus, we examined the therapeutic effect of the small-molecule Wnt inhibitor ICG-001 on cancer stemness and metastasis. The ICG-001 treatment efficiently attenuated self-renewal activity and metastatic potential. Mechanistically, myeloid ecotropic viral insertion site 1 (MEIS1) was identified as a target gene of ICG-001 that is transcriptionally regulated by Wnt signaling. A series of functional analyses revealed that MEIS1 enhanced the CSC behavior and metastatic potential of the CRC cells. Collectively, our findings suggest that ICG-001 efficiently inhibits CRC stemness and metastasis by suppressing MEIS1 expression. These results provide a basis for the further clinical investigation of ICG-001 as a targeted therapy for CSCs, opening a new avenue for the development of novel Wnt inhibitors for the treatment of CRC metastasis. |
| first_indexed | 2024-03-10T03:55:28Z |
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| id | doaj.art-46e68d74cb8e43cb9008e33c35c6c52f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:55:28Z |
| publishDate | 2021-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-46e68d74cb8e43cb9008e33c35c6c52f2023-11-23T08:45:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241341310.3390/ijms222413413The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 ExpressionJang-Hyun Choi0Tae-Young Jang1So-El Jeon2Jee-Heun Kim3Choong-Jae Lee4Hyeon-Ji Yun5Ji-Youn Jung6So-Yeon Park7Jeong-Seok Nam8School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaDepartment of Companion and Laboratory Animal Science, Kongju National University, Gongju 32439, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaSchool of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaRecurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been demonstrated to be more effective than existing chemotherapeutic drugs, resulting in a significant unmet need for effective CRC therapies. In this study, transcriptomic profiling of metastatic tumors from CRC patients revealed significant upregulation in the Wnt pathway and stemness genes. Thus, we examined the therapeutic effect of the small-molecule Wnt inhibitor ICG-001 on cancer stemness and metastasis. The ICG-001 treatment efficiently attenuated self-renewal activity and metastatic potential. Mechanistically, myeloid ecotropic viral insertion site 1 (MEIS1) was identified as a target gene of ICG-001 that is transcriptionally regulated by Wnt signaling. A series of functional analyses revealed that MEIS1 enhanced the CSC behavior and metastatic potential of the CRC cells. Collectively, our findings suggest that ICG-001 efficiently inhibits CRC stemness and metastasis by suppressing MEIS1 expression. These results provide a basis for the further clinical investigation of ICG-001 as a targeted therapy for CSCs, opening a new avenue for the development of novel Wnt inhibitors for the treatment of CRC metastasis.https://www.mdpi.com/1422-0067/22/24/13413colorectal cancercancer stem-like cellsmetastasisWntICG-001MEIS1 |
| spellingShingle | Jang-Hyun Choi Tae-Young Jang So-El Jeon Jee-Heun Kim Choong-Jae Lee Hyeon-Ji Yun Ji-Youn Jung So-Yeon Park Jeong-Seok Nam The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression International Journal of Molecular Sciences colorectal cancer cancer stem-like cells metastasis Wnt ICG-001 MEIS1 |
| title | The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression |
| title_full | The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression |
| title_fullStr | The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression |
| title_full_unstemmed | The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression |
| title_short | The Small-Molecule Wnt Inhibitor ICG-001 Efficiently Inhibits Colorectal Cancer Stemness and Metastasis by Suppressing MEIS1 Expression |
| title_sort | small molecule wnt inhibitor icg 001 efficiently inhibits colorectal cancer stemness and metastasis by suppressing meis1 expression |
| topic | colorectal cancer cancer stem-like cells metastasis Wnt ICG-001 MEIS1 |
| url | https://www.mdpi.com/1422-0067/22/24/13413 |
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