Loss of Epidermal Homeostasis Underlies the Development of Squamous Cell Carcinoma.

ABSTRACT

Squamous cell carcinoma (SCC) is one of the most common skin cancers. To develop targeted therapies for SCC, a comprehensive understanding of the disease through a systems approach is required. Here, we have collated and analyzed the literature on SCC and pathways that maintain skin homeostasis. Since, the loss of the Notch and the overactivation of the Wnt pathways in the epidermis cause SCC, we focused on these two pathways. We found that the two pathways are critical in maintaining epidermal homeostasis. Further, we found that the cancer stem cell (CSC) marker CD44 causes the transcription of SOX2, another CSC marker of SCC, activates the Wnt pathway, and blocks the Notch pathway. Similarly, the Wnt pathway causes the transcription of CD44 and SOX2 and blocks the Notch pathway. In this paper, we have discussed how the notch and the Wnt pathways affect epidermal homeostasis and the three CSCs (CD44, SOX2, and LGR6) affect the two pathways, linking the CSCs with epidermal homeostasis.