FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2
Abstract Purpose Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The Fat mass and obesity-associated protein (FTO), a genetic variant associated with obesity, significantly impact the energetic metabolism of mechanical tumors. However, research on the function of FT...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-01-01
|
| Series: | Journal of Cancer Research and Clinical Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s00432-024-06073-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823863263361761280 |
|---|---|
| author | Kongyan Zhang Fei Zhang Jiahe Wang |
| author_facet | Kongyan Zhang Fei Zhang Jiahe Wang |
| author_sort | Kongyan Zhang |
| collection | DOAJ |
| description | Abstract Purpose Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The Fat mass and obesity-associated protein (FTO), a genetic variant associated with obesity, significantly impact the energetic metabolism of mechanical tumors. However, research on the function of FTO in CRC is scarce. Methods Bioinformatics analysis of TCGA and UALCAN databases was conducted to examine FTO expression in CRC. Immunohistochemistry was used to assess FTO and PKM2 protein expression in clinical specimens. In vitro experiments utilized five human colon cancer cell lines and a normal colon epithelial cell line, with Western blotting and RT-PCR for protein and mRNA quantification, respectively, and lentiviral transfection to modulate FTO expression. Cellular behaviors such as proliferation, migration, invasion, and apoptosis were evaluated using various assays. Immunofluorescence and Seahorse Xfe96 metabolic analysis were employed to study PKM2 expression changes and glycolytic stress. The effects of PKM2 inhibition by shikonin on cell viability and glycolytic activity were assessed using CCK-8 assay and Seahorse analysis. Results An upregulation of FTO was observed in colon cancer through data mining and analysis of pathological specimens. Besides, we discovered that the impact of FTO on colon cancer glycolysis has significant implications for colon proliferation, invasion, and metastasis. The protein expression of PKM2 and the intensity of fluorescence staining in the nucleus of PKM2 were detected to be increased in colon carcinoma cells with over-expression of FTO. Conclusion FTO plays a significant role in CRC progression by regulating PKM2 and promoting glycolysis. |
| format | Article |
| id | doaj-art-4340436fa8394ed6b0d02f7deffa078f |
| institution | Kabale University |
| issn | 1432-1335 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Journal of Cancer Research and Clinical Oncology |
| spelling | doaj-art-4340436fa8394ed6b0d02f7deffa078f2025-02-09T12:10:12ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-01-01151111510.1007/s00432-024-06073-xFTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2Kongyan Zhang0Fei Zhang1Jiahe Wang2Department of Geriatrics, Fuyang Hospital of Anhui Medical UniversityDepartment of Family Medicine, Shengjing Hospital of China Medical UniversityDepartment of Family Medicine, Shengjing Hospital of China Medical UniversityAbstract Purpose Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The Fat mass and obesity-associated protein (FTO), a genetic variant associated with obesity, significantly impact the energetic metabolism of mechanical tumors. However, research on the function of FTO in CRC is scarce. Methods Bioinformatics analysis of TCGA and UALCAN databases was conducted to examine FTO expression in CRC. Immunohistochemistry was used to assess FTO and PKM2 protein expression in clinical specimens. In vitro experiments utilized five human colon cancer cell lines and a normal colon epithelial cell line, with Western blotting and RT-PCR for protein and mRNA quantification, respectively, and lentiviral transfection to modulate FTO expression. Cellular behaviors such as proliferation, migration, invasion, and apoptosis were evaluated using various assays. Immunofluorescence and Seahorse Xfe96 metabolic analysis were employed to study PKM2 expression changes and glycolytic stress. The effects of PKM2 inhibition by shikonin on cell viability and glycolytic activity were assessed using CCK-8 assay and Seahorse analysis. Results An upregulation of FTO was observed in colon cancer through data mining and analysis of pathological specimens. Besides, we discovered that the impact of FTO on colon cancer glycolysis has significant implications for colon proliferation, invasion, and metastasis. The protein expression of PKM2 and the intensity of fluorescence staining in the nucleus of PKM2 were detected to be increased in colon carcinoma cells with over-expression of FTO. Conclusion FTO plays a significant role in CRC progression by regulating PKM2 and promoting glycolysis.https://doi.org/10.1007/s00432-024-06073-xFTOPKM2Colon cancerGlycolytic metabolismTherapeutic target |
| spellingShingle | Kongyan Zhang Fei Zhang Jiahe Wang FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 Journal of Cancer Research and Clinical Oncology FTO PKM2 Colon cancer Glycolytic metabolism Therapeutic target |
| title | FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 |
| title_full | FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 |
| title_fullStr | FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 |
| title_full_unstemmed | FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 |
| title_short | FTO effects the proliferation, invasion, and glycolytic metabolism of colon cancer by regulating PKM2 |
| title_sort | fto effects the proliferation invasion and glycolytic metabolism of colon cancer by regulating pkm2 |
| topic | FTO PKM2 Colon cancer Glycolytic metabolism Therapeutic target |
| url | https://doi.org/10.1007/s00432-024-06073-x |
| work_keys_str_mv | AT kongyanzhang ftoeffectstheproliferationinvasionandglycolyticmetabolismofcoloncancerbyregulatingpkm2 AT feizhang ftoeffectstheproliferationinvasionandglycolyticmetabolismofcoloncancerbyregulatingpkm2 AT jiahewang ftoeffectstheproliferationinvasionandglycolyticmetabolismofcoloncancerbyregulatingpkm2 |