Molecular Mechanisms of Cutaneous Squamous Cell Carcinoma

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Apr 12

PMID 35408839

Authors

Matthew L Hedberg

Corbett T Berry

Ata S Moshiri

Yan Xiang

Christopher J Yeh

Cem Attilasoy

Brian C Capell

John T Seykora

Affiliations

Soon will be listed here.

Abstract

Non-melanoma skin cancers are cutaneous malignancies representing the most common form of cancer in the United States. They are comprised predominantly of basal cell carcinomas and squamous cell carcinomas (cSCC). The incidence of cSCC is increasing, resulting in substantial morbidity and ever higher treatment costs; currently in excess of one billion dollars, per annum. Here, we review research defining the molecular basis and development of cSCC that aims to provide new insights into pathogenesis and drive the development of novel, cost and morbidity saving therapies.

Citing Articles

Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4 Pathway via the p300-p53 Axis.

Huang X, Wang W, Zhang S, Li L, Huang J Biomol Ther (Seoul). 2025; 33(2):365-377.

PMID: 39989046 PMC: 11893488. DOI: 10.4062/biomolther.2024.156.

From actinic keratosis to cutaneous squamous cell carcinoma: the key pathogenesis and treatments.

Li Z, Lu F, Zhou F, Song D, Chang L, Liu W Front Immunol. 2025; 16:1518633.

PMID: 39925808 PMC: 11802505. DOI: 10.3389/fimmu.2025.1518633.

The Role of the Large T Antigen in the Molecular Pathogenesis of Merkel Cell Carcinoma.

Myrda J, Bremm F, Schaft N, Dorrie J Genes (Basel). 2024; 15(9).

PMID: 39336718 PMC: 11431464. DOI: 10.3390/genes15091127.

The Mutational and Microenvironmental Landscape of Cutaneous Squamous Cell Carcinoma: A Review.

Hosseini T, Park S, Guo T Cancers (Basel). 2024; 16(16).

PMID: 39199674 PMC: 11352924. DOI: 10.3390/cancers16162904.

Studies on Human Cultured Fibroblasts and Cutaneous Squamous Cell Carcinomas Suggest That Overexpression of Histone Variant H2A.J Promotes Radioresistance and Oncogenic Transformation.

Freyter B, Abd Al-Razaq M, Hecht M, Rube C, Rube C Genes (Basel). 2024; 15(7).

PMID: 39062630 PMC: 11275829. DOI: 10.3390/genes15070851.

References

Rezvani H, Rossignol R, Ali N, Benard G, Tang X, Yang H . XPC silencing in normal human keratinocytes triggers metabolic alterations through NOX-1 activation-mediated reactive oxygen species. Biochim Biophys Acta. 2010; 1807(6):609-19. PMC: 3086958. DOI: 10.1016/j.bbabio.2010.12.006. View

Yang X, Daifallah A, Shankar S, Beer J, Marshall C, Dentchev T . Topical kinase inhibitors induce regression of cutaneous squamous cell carcinoma. Exp Dermatol. 2019; 28(5):609-613. PMC: 6520110. DOI: 10.1111/exd.13902. View

Brash D . UV signature mutations. Photochem Photobiol. 2014; 91(1):15-26. PMC: 4294947. DOI: 10.1111/php.12377. View

Wang Y, Sun B, Wen X, Hao D, Du D, He G . The Roles of lncRNA in Cutaneous Squamous Cell Carcinoma. Front Oncol. 2020; 10:158. PMC: 7059100. DOI: 10.3389/fonc.2020.00158. View

Li Y, Hanna G, Laga A, Haddad R, Lorch J, Hammerman P . Genomic analysis of metastatic cutaneous squamous cell carcinoma. Clin Cancer Res. 2015; 21(6):1447-56. PMC: 4359951. DOI: 10.1158/1078-0432.CCR-14-1773. View

Zhou L, Wang Y, Zhou M, Zhang Y, Wang P, Li X . HOXA9 inhibits HIF-1α-mediated glycolysis through interacting with CRIP2 to repress cutaneous squamous cell carcinoma development. Nat Commun. 2018; 9(1):1480. PMC: 5902613. DOI: 10.1038/s41467-018-03914-5. View

Mandinova A, Lefort K, Tommasi di Vignano A, Stonely W, Ostano P, Chiorino G . The FoxO3a gene is a key negative target of canonical Notch signalling in the keratinocyte UVB response. EMBO J. 2008; 27(8):1243-54. PMC: 2367396. DOI: 10.1038/emboj.2008.45. View

Vanbokhoven H, Melino G, Candi E, Declercq W . p63, a story of mice and men. J Invest Dermatol. 2011; 131(6):1196-207. DOI: 10.1038/jid.2011.84. View

Nessa A, Rashid M, E-Ferdous N, Chowdhury A . Screening for and management of high-grade cervical intraepithelial neoplasia in Bangladesh: a cross-sectional study comparing two protocols. J Obstet Gynaecol Res. 2012; 39(2):564-71. DOI: 10.1111/j.1447-0756.2012.01998.x. View

10.

Thomson J, Bewicke-Copley F, Anene C, Gulati A, Nagano A, Purdie K . The Genomic Landscape of Actinic Keratosis. J Invest Dermatol. 2021; 141(7):1664-1674.e7. PMC: 8221374. DOI: 10.1016/j.jid.2020.12.024. View

11.

Mardaryev A, Liu B, Rapisarda V, Poterlowicz K, Malashchuk I, Rudolf J . Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium. J Cell Biol. 2015; 212(1):77-89. PMC: 4700479. DOI: 10.1083/jcb.201506065. View

12.

Petitjean A, Ruptier C, Tribollet V, Hautefeuille A, Chardon F, Cavard C . Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with DeltaNp73. Carcinogenesis. 2007; 29(2):273-81. DOI: 10.1093/carcin/bgm258. View

13.

Lima P, Joseph S, Panizza B, Simpson F . Epidermal Growth Factor Receptor's Function in Cutaneous Squamous Cell Carcinoma and Its Role as a Therapeutic Target in the Age of Immunotherapies. Curr Treat Options Oncol. 2020; 21(1):9. DOI: 10.1007/s11864-019-0697-3. View

14.

Li Y, Seto E . HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring Harb Perspect Med. 2016; 6(10). PMC: 5046688. DOI: 10.1101/cshperspect.a026831. View

15.

Fernandez-Figueras M, Saenz-Sarda X, Vargas P, Thompson C, Carrato C, Puig L . The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment. J Eur Acad Dermatol Venereol. 2018; 32(10):1657-1661. DOI: 10.1111/jdv.14901. View

16.

Chitsazzadeh V, Coarfa C, Drummond J, Nguyen T, Joseph A, Chilukuri S . Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates. Nat Commun. 2016; 7:12601. PMC: 5013636. DOI: 10.1038/ncomms12601. View

17.

Kathpalia V, Mussak E, Chow S, Lam P, Skelley N, Time M . Genome-wide transcriptional profiling in human squamous cell carcinoma of the skin identifies unique tumor-associated signatures. J Dermatol. 2006; 33(5):309-18. DOI: 10.1111/j.1346-8138.2006.00075.x. View

18.

Sartini D, Campagna R, Lucarini G, Pompei V, Salvolini E, Mattioli-Belmonte M . Differential immunohistochemical expression of paraoxonase-2 in actinic keratosis and squamous cell carcinoma. Hum Cell. 2021; 34(6):1929-1931. DOI: 10.1007/s13577-021-00581-5. View

19.

Corchado-Cobos R, Garcia-Sancha N, Gonzalez-Sarmiento R, Perez-Losada J, Canueto J . Cutaneous Squamous Cell Carcinoma: From Biology to Therapy. Int J Mol Sci. 2020; 21(8). PMC: 7216042. DOI: 10.3390/ijms21082956. View

20.

Li Z, Razavi P, Li Q, Toy W, Liu B, Ping C . Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway. Cancer Cell. 2018; 34(6):893-905.e8. PMC: 6294301. DOI: 10.1016/j.ccell.2018.11.006. View