FOXM1 Upregulation Is an Early Event in Human Squamous Cell Carcinoma and it Is Enhanced by Nicotine during Malignant Transformation

We have shown for the first time that overexpression of FOXM1 precedes head and neck squamous cell carcinoma malignancy

Emilios Gemenetzidis; Amrita Bose; Adeel M. Riaz; Tracy Chaplin; Bryan D. Young; Muhammad Ali; David Sugden; Johanna K. Thurlow; Sok-Ching Cheong; Soo-Hwang Teo; Hong Wan; Ahmad Waseem; Eric K. Parkinson; Farida Fortune; Muy-Teck Teh

2009

Scholarcy highlights

  • The forkhead box protein family of transcription factors exhibit a myriad of biological functions such as regulation of cell cycle, proliferation, apoptosis, differentiation and longevity during embryonic development and adult tissue homeostasis
  • We originally established a link between FOXM1 and tumourigenesis when we demonstrated that FOXM1 was a downstream target of Gli1 in basal cell carcinoma and showed that of the three known alternatively spliced isoforms, FOXM1B isoform was overexpressed in BCCs
  • Our bioinformatics analysis based on a panel of microarray data showed that FOXM1 mRNA expression was significantly upregulated in both premalignant dysplastic lesions and head and neck squamous cell carcinoma compared to normal oral mucosa
  • The FOXM1 transcription factor is commonly overexpressed in a variety of human malignancies and several studies have suggested that this may be associated with malignant transformation
  • This study provided the first evidence that FOXM1 is upregulated in oral dysplasias and HNSCC samples collected from various geographically distinct patient cohorts consisting of both Caucasians and Asians
  • The co-carcinogenic effect of nicotine supports the finding that the risk of developing HNSCC is increased to 15 times higher in patients chewing betel quid with tobacco compared to chewing betel quid alone
  • The synergistic action of nicotine and FOXM1B overexpression led to anchorage-independent malignant transformation of a premalignant oral keratinocyte line which exhibited non-random genomic instability loss of heterozygosity/copy number abnormality profiles

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