The Grainyhead-Like Transcription Factor 3 Expression Pattern in Relation to the Caveolin 1/ Mammalian Target of Rapamycin (mTOR) Axis in Non-Melanoma Skin Cancer

Background: Non-melanoma skin cancers (NMSCs), including both basal and squamous cell carcinoma, have increasing incidence worldwide. The grainyhead-like transcription factor-3 (GRHL3) is involved in skin barrier formation and wound healing. Caveolin 1 (cav-1)/mammalian target of rapamycin (mTOR) axis is implicated in different malignancies.
Objective: The study aimed to assess the expression pattern of GRHL3 in NMSCs and its correlation with cav-1/mTOR signaling pathway.
Patients and methods: The study involved twenty NMSC patients. Group1 was subdivided into groups 1a and 1b, which had tumour tissue from basal cell carcinoma (12 patients) and squamous cell carcinoma (8 patients) respectively. Group 2 had tissue of safety margin of same patients, and was also subdivided into 2a, and 2b groups. The levels of cav-1, malondialdehyde, total anti-oxidant capacity, and the gene expression levels of GRHL3, mTOR, autophagy-related gene 7 (ATG7) were assayed in the tumour tissue and the nearby safety margin. The immunohistochemical expression of cav-1 was determined.
Results: The study showed upregulation of the levels of malondialdehyde, and the gene expression levels of mTOR, and ATG7 in tumour tissue compared to tissue of safety margin. On the other hand, it showed downregulation of caveolin 1, total anti-oxidant capacity, and gene expression levels of GRHL3 in tumour tissue compared to safety margin tissue. Both GRHL3 and cav-1 showed significant negative correlation with mTOR and ATG7.
Conclusion: GRHL3 and cav-1 might have tumour suppressor effects. Oxidative stress might trigger mTOR signaling. The rise of the gene expression levels of mTOR and ATG7 indicates autophagy activation in basal and squamous cell carcinoma. Cav-1 might have inhibitory effect on autophagy.