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| Open Access
Uncovering the complex relationship between balding, testosterone and skin cancers in men
Male-pattern baldness (MPB) is related to dysregulation of androgens. Here, authors show that MPB (but not androgens) is associated with skin cancer risk, particularly in the scalp region, suggesting that sun exposure, rather than androgens, is the main driver.
- Jue-Sheng Ong
- , Mathias Seviiri
- & Matthew H. Law
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| Open Access
Functionally distinct cancer-associated fibroblast subpopulations establish a tumor promoting environment in squamous cell carcinoma
During the progression of cutaneous squamous cell carcinoma (cSCC), dermal fibroblasts become activated into cancer-associated fibroblasts (CAFs) which are pro-tumorigenic. Here, using single-cell RNA sequencing of patients’ samples at different stages of cSCC progression, the authors identify two main CAF subsets and deduce their potential functions using bioinformatics.
- Sabrina Schütz
- , Llorenç Solé-Boldo
- & Frank Lyko
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| Open Access
Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression
The process by which actinic keratosis differentiates to malignant invasive cutaneous squamous cell carcinoma is unclear. Here, the authors use RNA-seq to illustrate a disease continuum between the two states, and use in vivo models to confirm the role of Tgfbr2, Trp53, and Notch1 in this process.
- Peter Bailey
- , Rachel A. Ridgway
- & Gareth J. Inman
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Article
| Open Access
The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma
TINCR encodes a p53-regulated ubiquitin-like microprotein expressed in stratified epithelia. Tincr loss promotes UVB-induced skin carcinogenesis in mice and deletions and mutations in human squamous cell carcinoma support a tumor suppressor role.
- Lucia Morgado-Palacin
- , Jessie A. Brown
- & Adolfo A. Ferrando
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Article
| Open Access
The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome
The identification of kinases that control epigenetic mechanisms in squamous cell carcinomas (SCCs) can be of therapeutic relevance. Here the authors show that loss of nuclear kinase ULK3 impairs the recruitment of two histone arginine methyltransferases, PRMT1 and PRMT5 to the promoter regions of genes of functions, hence, suppressing the tumorigenic potential of SCC cells.
- Sandro Goruppi
- , Andrea Clocchiatti
- & G. Paolo Dotto
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| Open Access
Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues
Squamous cell carcinomas are an aggressive cancer type which can occur in multiple organ systems. Here, the authors analyse the proteome of SCC cancers from 17 organs and show commonly dysregulated proteins independent of location.
- Qi Song
- , Ye Yang
- & Yingyong Hou
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| Open Access
Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer
The relevance and underlying molecular mechanisms of epigenetic regulation in squamous cell carcinomas (SCC) await further characterization. Here, the authors show a transcriptional regulatory loop involving SREBF1, TP63 and KLF5 driving tumourigenesis in SCC through fatty acid, ERBB and mTOR pathway regulation.
- Li-Yan Li
- , Qian Yang
- & De-Chen Lin
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Article
| Open Access
Autophagy of the m6A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis
RNA m6A demethylase FTO has oncogenic roles in cancers. Here the authors show that chronic low-level exposure of arsenic inhibits autophagic degradation of FTO, leading to FTO stabilisation and reduced m6A RNA methylation in keratinocytes and its subsequent malignant transformation.
- Yan-Hong Cui
- , Seungwon Yang
- & Yu-Ying He
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Article
| Open Access
Disease risk scores for skin cancers
Predicting who will develop skin cancer is difficult. Here, the authors from 23andMe developed a polygenic risk score for skin cancer based on a questionnaire and genetic data from more than 210,000 individuals and suggest that the score could be used in early screening programmes.
- Pierre Fontanillas
- , Babak Alipanahi
- & Adam Auton
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| Open Access
NOTCH1 gene amplification promotes expansion of Cancer Associated Fibroblast populations in human skin
The presence of genomic alterations in cancer associated fibroblasts (CAFs) is largely unexplored. The authors show that frequent NOTCH1 gene amplification and overexpression render CAFs resistant to the UVA-induced DNA damage response (DDR) and promote cancer/stromal cells expansion, which can be reversed by NOTCH inhibition.
- Atul Katarkar
- , Giulia Bottoni
- & G. Paolo Dotto
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Article
| Open Access
CSL controls telomere maintenance and genome stability in human dermal fibroblasts
Conversion of dermal fibroblasts into Cancer Associated Fibroblasts (CAFs) can play an important role in keratinocyte tumour development. Here the authors reveal that CSL plays a role in maintenance of telomeres and genomic integrity in both dermal fibroblasts and CAFs.
- Giulia Bottoni
- , Atul Katarkar
- & G. Paolo Dotto
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Article
| Open Access
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin
Most tumours are characterized by increased aerobic glycolytic activity. Here the authors show that elevated aerobic glycolysis is not essential for cancer initiation by testing the effect of lactate dehydrogenase depletion on the ability of hair follicle stem cells (HFSCs) to form squamous cell carcinoma (SCC) in mouse genetic models.
- A. Flores
- , S. Sandoval-Gonzalez
- & W. E. Lowry
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Article
| Open Access
Bone marrow-derived epithelial cells and hair follicle stem cells contribute to development of chronic cutaneous neoplasms
Bone marrow-derived epithelial cells can be recruited to sites of chronic inflammation. Here, the authors using allogenic bone marrow transplantation in a multistage murine cutaneous carcinogenesis model show that bone marrow-derived epithelial cells and hair follicle stem cells are recruited to cutaneous neoplasms during tumor promotion of carcinogen-exposed skin and bone marrow.
- Heuijoon Park
- , Sonali Lad
- & Rebecca J. Morris
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Article
| Open AccessGene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma
Genetic loci linked to susceptibility for the common skin cancer cutaneous squamous cell carcinoma (cSCC) have been identified by genome wide association studies (GWAS). Here, the authors impute gene expression levels from GWAS data to perform a transcriptome wide association study (TWAS), identifying five novel genetic loci linked to cSCC susceptibility.
- Nilah M. Ioannidis
- , Wei Wang
- & Alice S. Whittemore
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| Open Access
The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature
It is known cutaneous squamous cell carcinoma (cSCC) involves a high tumour mutation burden. Here the authors identify common cSCC mutated genes, copy number changes, altered pathways and report the presence of a novel mutation signature associated with chronic exposure to the immunosuppressive drug azathioprine.
- Gareth J. Inman
- , Jun Wang
- & Irene M. Leigh
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Article
| Open Access
HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development
Hypoxia-inducible transcription factor HIF-1α promotes glycolysis allowing cell survival under stress. Here the authors show, using both cell lines and animal models, that in cutaneous squamous cell carcinoma HOXA9 acts as a tumor suppressor and inhibits glycolysis by associating with CRIP2 to repress HIF-1α binding to target genes.
- Liang Zhou
- , Yinghui Wang
- & Zhenhua Ding
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| Open Access
Methylation profiling identifies two subclasses of squamous cell carcinoma related to distinct cells of origin
Cutaneous squamous cell carcinoma (cSCC) is a skin cancer that normally progresses from UV-induced actinic keratosis (AK). Here, the authors investigate the epigenomics of cSCC and highlight two distinct subclasses of AK and cSCC originating from distinct keratinocyte differentiation stages.
- Manuel Rodríguez-Paredes
- , Felix Bormann
- & Frank Lyko
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| Open Access
Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates
Cutaneous squamous cell of the skin is a common neoplasm that frequently arises from precancerous actinic keratoses. Here, the authors carry out genomic analysis on matched sets of human lesions and compare with those in ultraviolet treated mice and identify conserved drivers of tumour development.
- Vida Chitsazzadeh
- , Cristian Coarfa
- & Kenneth Y. Tsai
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| Open Access
Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma
Cutaneous squamous cell carcinoma is the second most common type of skin cancer. In this genome-wide association study, which includes over 7,000 cases, the authors identify 4 new susceptibility loci for this cancer and also provide independent replication of 9 previously reported susceptibility loci.
- Harvind S. Chahal
- , Yuan Lin
- & Kavita Y. Sarin
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SOX2 is a cancer-specific regulator of tumour initiating potential in cutaneous squamous cell carcinoma
The mechanisms that sustain the self-renewal and expansion of cancer cells with tumour initiating potential are not completely understood. Here the authors show that the transcription factor, Sox2, marks tumour initiating cells in cutaneous squamous cell carcinomas and is required for their expansion.
- Jasmin M. Siegle
- , Alice Basin
- & Markus Schober
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Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia
The transcription factor Nanog regulates self-renewal in pluripotent stem cells and cancer stem cells. Here the authors show that Nanog is expressed in mouse adult stratified epithelia, and its overexpression increases proliferation and aneuploidy and activates pathways associated to mitosis.
- Daniela Piazzolla
- , Adelaida R. Palla
- & Manuel Serrano
ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation