Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells
Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from sphe...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/12/5/668 |
| _version_ | 1797501274998964224 |
|---|---|
| author | Peng Ye Xiaoxia Chi Xiuwen Yan Fangqin Wu Zhigang Liang Wen-Hao Yang |
| author_facet | Peng Ye Xiaoxia Chi Xiuwen Yan Fangqin Wu Zhigang Liang Wen-Hao Yang |
| author_sort | Peng Ye |
| collection | DOAJ |
| description | Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine–glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration. |
| first_indexed | 2024-03-10T03:16:02Z |
| format | Article |
| id | doaj.art-e3e3696d1f2d4db98e88834b768938b4 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T03:16:02Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-e3e3696d1f2d4db98e88834b768938b42023-11-23T10:13:49ZengMDPI AGBiomolecules2218-273X2022-05-0112566810.3390/biom12050668Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma CellsPeng Ye0Xiaoxia Chi1Xiuwen Yan2Fangqin Wu3Zhigang Liang4Wen-Hao Yang5Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, ChinaKey Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, ChinaKey Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, ChinaKey Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 910095, ChinaKey Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, ChinaKey Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes and Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou 910095, ChinaLiver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine–glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.https://www.mdpi.com/2218-273X/12/5/668hepatocellular carcinomacancer stem cellsAGXTSOX2OCT4 |
| spellingShingle | Peng Ye Xiaoxia Chi Xiuwen Yan Fangqin Wu Zhigang Liang Wen-Hao Yang Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells Biomolecules hepatocellular carcinoma cancer stem cells AGXT SOX2 OCT4 |
| title | Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells |
| title_full | Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells |
| title_fullStr | Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells |
| title_short | Alanine–Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells |
| title_sort | alanine glyoxylate aminotransferase sustains cancer stemness properties through the upregulation of sox2 and oct4 in hepatocellular carcinoma cells |
| topic | hepatocellular carcinoma cancer stem cells AGXT SOX2 OCT4 |
| url | https://www.mdpi.com/2218-273X/12/5/668 |
| work_keys_str_mv | AT pengye alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells AT xiaoxiachi alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells AT xiuwenyan alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells AT fangqinwu alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells AT zhigangliang alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells AT wenhaoyang alanineglyoxylateaminotransferasesustainscancerstemnesspropertiesthroughtheupregulationofsox2andoct4inhepatocellularcarcinomacells |