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...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-05, Vol.12 (5), p.668
Main Authors: Ye, Peng, Chi, Xiaoxia, Yan, Xiuwen, Wu, Fangqin, Liang, Zhigang, Yang, Wen-Hao
Format: Article
Language:English
Subjects:
AGXT
Alanine
Amino acids
Antibodies
Biomarkers
cancer stem cells
Cancer therapies
Carcinoma, Hepatocellular - metabolism
Cell Line, Tumor
Cell self-renewal
Drug resistance
Genes
Growth factors
Hepatocellular carcinoma
Hepatocytes
Humans
Kinases
Liver cancer
Liver Neoplasms - metabolism
Medical prognosis
Metabolism
Metastases
Oct-4 protein
OCT4
Polymerase chain reaction
Proteins
Software
SOX2
SOXB1 Transcription Factors - genetics
SOXB1 Transcription Factors - metabolism
Spheroids
Stem cells
Transaminases
Transcription factors
Transcriptomics
Tumors
Up-Regulation
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Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12050668