Transcriptional repression of SOX2 by p53 in cancer cells regulates cell identity and migration
Article Swipe
Patricia Lado‐Fernández
,
Jéssica M. Vilas
,
Tânia Fernandes
,
Carmen Carneiro
,
Sabela Da Silva‐Álvarez
,
Valentín Estévez‐Souto
,
Pablo Pedrosa
,
Miguel González‐Barcia
,
Luis E. Abatti
,
Jennifer A. Mitchell
,
Carmen Rivas
,
Gema Moreno‐Bueno
,
Anxo Vidal
,
Manuel Collado
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ijc.35490
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1002/ijc.35490
During cancer development and progression, many genetic alterations lead to the acquisition of novel features that confer selective advantage to cancer cells and that resemble developmental programs. SRY‐box transcription factor 2 (SOX2) is one of the key pluripotency transcription factors, expressed during embryonic development and active in adult stem cells. In cancer, SOX2 is frequently dysregulated and associated with tumor stemness and poor patient survival. SOX2 expression is suppressed in differentiated cells by tumor suppressor proteins that form a transcriptional repressive complex. We previously identified some of these proteins and found that their absence combined with deficiency in Trp53 leads to maximal dysregulated expression of Sox2 . Using cancer cell lines of different origin and with different p53 status, we show here that manipulating TP53 to restore or decrease its activity results in repression or induction of SOX2 , respectively. Mechanistically, we observed that the regulation of SOX2 expression by TP53 is transcriptional and identified Trp53 bound to the promoter region and the Sox2 Regulatory Region 2 enhancer of Sox2 . Forcing high levels of SOX2 in cancer cells leads to morphological changes that molecularly correspond to the acquisition of a more mesenchymal phenotype, correlating with an increased migratory capacity. Finally, the analysis of human breast cancer samples shows that this correlation between TP53 status, levels of expression of SOX2 , and a more metastatic phenotype is also observed in cancer patients. Our results support the notion that lack of TP53 in tumor cells results in deregulated expression of developmental gene SOX2 with phenotypic consequences related to increased malignization.
Related Topics
Concepts
Psychological repression
SOX2
Cell migration
Identity (music)
Cell
Biology
Cell biology
Cancer research
Genetics
Gene
Transcription factor
Gene expression
Art
Aesthetics
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/ijc.35490
- https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.35490
- OA Status
- hybrid
- Cited By
- 2
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4410944253
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4410944253Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/ijc.35490Digital Object Identifier
- Title
-
Transcriptional repression of
SOX2 by p53 in cancer cells regulates cell identity and migrationWork title - Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-06-02Full publication date if available
- Authors
-
Patricia Lado‐Fernández, Jéssica M. Vilas, Tânia Fernandes, Carmen Carneiro, Sabela Da Silva‐Álvarez, Valentín Estévez‐Souto, Pablo Pedrosa, Miguel González‐Barcia, Luis E. Abatti, Jennifer A. Mitchell, Carmen Rivas, Gema Moreno‐Bueno, Anxo Vidal, Manuel ColladoList of authors in order
- Landing page
-
https://doi.org/10.1002/ijc.35490Publisher landing page
- PDF URL
-
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.35490Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.35490Direct OA link when available
- Concepts
-
Psychological repression, SOX2, Cell migration, Identity (music), Cell, Biology, Cell biology, Cancer research, Genetics, Gene, Transcription factor, Gene expression, Art, AestheticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
-
38Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| cited_by_percentile_year.max | 97 |
| cited_by_percentile_year.min | 95 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 14 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/1 |
| sustainable_development_goals[0].score | 0.5600000023841858 |
| sustainable_development_goals[0].display_name | No poverty |
| citation_normalized_percentile.value | 0.90172939 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |