ArticleOncogene2018
Epigenetically regulated PAX6 drives cancer cells toward a stem-like state via GLI-SOX2 signaling axis in lung adenocarcinoma.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Circulating cell-free DNA methylation as biomarker for lung cancer detection: a systematic review and meta-analysis of diagnostic studies.Systematic reviews · 2025Pooled it
- Inhibition of Pax6 sumoylation suppresses the tumorigenicity of pancreatic cancer cells.Cell death and differentiation · 2026Article
- Network-based single-cell analysis identifies a proliferative GZMBJournal of translational medicine · 2026Article
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- One section, two worlds: single-cell integration of MALDI-MSI and spatial transcriptomics on the same single tissue section.Scientific reports · 2025Article
- Proteogenomic profiling of soft tissue leiomyosarcoma reveals distinct molecular subtypes with divergent outcomes and therapeutic vulnerabilities.bioRxiv : the preprint server for biology · 2025Article
- PAX Family, Master Regulator in Cancer.Diagnostics (Basel, Switzerland) · 2025Review
- PAX6 enhances Nanog expression by inhibiting NOTCH signaling to promote malignant properties in small cell lung cancer cells.Heliyon · 2025Article
- A cutting-edge investigation of the multifaceted role of SOX family genes in cancer pathogenesis through the modulation of various signaling pathways.Functional & integrative genomics · 2025Review
- PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.Journal of experimental & clinical cancer research : CR · 2024Article
- LncRNA MIR31HG fosters stemness malignant features of non-small cell lung cancer via H3K4me1- and H3K27Ace-mediated GLI2 expression.Oncogene · 2024Article
- Transcriptional regulation of cancer stem cell: regulatory factors elucidation and cancer treatment strategies.Journal of experimental & clinical cancer research : CR · 2024Review
- PARD3 drives tumorigenesis through activating Sonic Hedgehog signalling in tumour-initiating cells in liver cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
- ADAMTS9-AS1 Long Non‑coding RNA Sponges miR‑128 and miR-150 to Regulate Ras/MAPK Signaling Pathway in Glioma.Cellular and molecular neurobiology · 2023Article
- HOPX is a tumor-suppressive biomarker that corresponds to T cell infiltration in skin cutaneous melanoma.Cancer cell international · 2023Article
- Review
- Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin-Induced Resistance and Stemness in Human Lung Cancer A549 Cells.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Expression analysis and regulation of GLI and its correlation with stemness and metabolic alteration in human brain tumor.3 Biotech · 2023Article
- The transcription factor PAX8 promotes angiogenesis in ovarian cancer through interaction with SOX17.Science signaling · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
It remains unclear whether PAX6 acts as a crucial transcription factor for lung cancer stem cell (CSC) traits. We demonstrate that PAX6 acts as an oncogene responsible for induction of cancer stemness properties in lung adenocarcinoma (LUAD). Mechanistically, PAX6 promotes GLI transcription, resulting in SOX2 upregulation directly by the binding of GLI to the proximal promoter region of the SOX2 gene. The overexpressed SOX2 enhances the expression of key pluripotent factors (OCT4 and NANOG) and suppresses differentiation lineage factors (HOPX and NKX2-1), driving cancer cells toward a stem-like state. In contrast, in the differentiated non-CSCs, PAX6 is transcriptionally silenced by its promoter methylation. In human lung cancer tissues, the positive linear correlations of PAX6 expression with GLI and SOX2 expression and its negative correlations with HOPX and NKX2-1 expression were observed. Therapeutically, the blockade of the PAX6-GLI-SOX2 signaling axis elicits a long-lasting therapeutic efficacy by limiting CSC expansion following chemotherapy. Furthermore, a methylation panel including the PAX6 gene yielded a sensitivity of 79.1% and specificity of 83.3% for cancer detection using serum DNA from stage IA LUAD. Our findings provide a rationale for targeting the PAX6-GLI-SOX2 signaling axis with chemotherapy as an effective therapeutic strategy and support the clinical utility of PAX6 gene promoter methylation as a biomarker for early lung cancer detection.
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