A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

Melath, Anil; Santhakumar, Gopi Krishnan; Madhavannair, Shyam Sunder; Nedumgottil, Binoy Mathews; Ramanathan, Arvind

doi:10.7314/apjcp.2013.14.11.6803

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…A fraction of non-syndromic and syndromic CLP patients harbors pathological IRF6 or GRHL3 variants that result in loss of their regular activities as transcription factors. As such, it is notable that in case of IRF6 , identical variants have also been identified in head and neck SCCs ( 42 , 43 ). Despite this discovery, the roles of IRF6 and GRHL3 in cancers remain controversial as both factors have been described as oncogenes and tumor suppressors ( Supplementary Table 4 ).…”

Section: Discussionmentioning

confidence: 99%

Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas

Parisi

Mockenhaupt²,

Rihs³

et al. 2022

Front. Oncol.

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Interferon Regulatory Factor 6 (IRF6) and Grainyhead Like Transcription Factor 3 (GRHL3) are transcription factors that orchestrate gene regulatory networks required for the balance between keratinocyte differentiation and proliferation. Absence of either protein results in the lack of a normal stratified epidermis with keratinocytes failing to stop proliferating and to terminally differentiate. Numerous pathological variants within IRF6 and GRHL3 have been identified in orofacial cleft-affected individuals and expression of the two transcription factors has been found to be often dysregulated in cancers. However, whether orofacial cleft-associated IRF6 and GRHL3 variants in patients might also affect their cancer risk later in life, is not clear yet. The fact that the role of IRF6 and GRHL3 in cancer remains controversial makes this question even more challenging. Some studies identified IRF6 and GRHL3 as oncogenes, while others could attribute tumor suppressive functions to them. Trying to solve this apparent conundrum, we herein aimed to characterize IRF6 and GRHL3 function in various types of carcinomas. We screened multiple cancer and normal cell lines for their expression, and subsequently proceeded with functional assays in cancer cell lines. Our data uncovered consistent downregulation of IRF6 and GRHL3 in all types of carcinomas analyzed. Reduced levels of IRF6 and GRHL3 were found to be associated with several tumorigenic properties, such as enhanced cell proliferation, epithelial mesenchymal transition, migration and reduced differentiation capacity. Based on our findings, IRF6 and GRHL3 can be considered as tumor suppressor genes in various carcinomas, which makes them potential common etiological factors for cancer and CLP in a fraction of CLP-affected patients.

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Section: Discussionmentioning

confidence: 99%

Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas

Parisi

Mockenhaupt²,

Rihs³

et al. 2022

Front. Oncol.

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Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer

Freitas

Machado

Santos

et al. 2019

Archives of Oral Biology

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Oral lichen planus: A chronic inflammatory model to study the regulation of the Toll-like receptor signaling in oral keratinocytes

Osorio-Osorno

Parada-Sanchez

Arango

et al. 2020

Journal of Oral Biosciences

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A Novel Heterozygous Mutation (F252Y) in Exon 7 of the IRF6 Gene is Associated with Oral Squamous Cell Carcinomas

Abstract: Keywords: IRF6 -IRF6 mutation -IRF6 mutation in oral cancer -IRF6 mutation in Indian cancer

Cited by 3 publications

References 25 publications

Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas

Consistent downregulation of the cleft lip/palate-associated genes IRF6 and GRHL3 in carcinomas

Polymorphisms associated with oral clefts as potential susceptibility markers for oral and breast cancer

Oral lichen planus: A chronic inflammatory model to study the regulation of the Toll-like receptor signaling in oral keratinocytes

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