ArticleCell death & disease2017
Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- The human Flower isoform hFWE4 facilitates cornification in cutaneous squamous cell carcinoma.JID innovations : skin science from molecules to population health · 2026Article
- Sumo-regulatory SENP2 controls the homeostatic squamous mitosis-differentiation checkpoint.Cell death & disease · 2024Article
- DNA damage signalling histone H2AX is required for tumour growth.Cell death discovery · 2024Article
- Metabolomic Analysis of Actinic Keratosis and SCC Suggests a Grade-Independent Model of Squamous Cancerization.Cancers · 2021Article
- Article
- TEX10 Promotes the Tumorigenesis and Radiotherapy Resistance of Urinary Bladder Carcinoma by Stabilizing XRCC6.Journal of immunology research · 2021Article
- Review
- The DNA damage response links human squamous proliferation with differentiation.The Journal of cell biology · 2020Article
- β-HPV 8E6 combined with TERT expression promotes long-term proliferation and genome instability after cytokinesis failure.Virology · 2020Article
- Mammalian endoreplication emerges to reveal a potential developmental timer.Cell death and differentiation · 2018Review
- Tex10 is upregulated and promotes cancer stem cell properties and chemoresistance in hepatocellular carcinoma.Cell cycle (Georgetown, Tex.) · 2018Article
- FOXM1 allows human keratinocytes to bypass the oncogene-induced differentiation checkpoint in response to gain of MYC or loss of p53.Oncogene · 2017Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy.
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