**4. Conclusion**

Apoptosis is a critical cellular process to protect keratinocytes during skin tumor initiation. Environmental assaults induce a mutation in a critical gene or genes. Apoptosis can remove DNA-damaged keratinocytes that are not repaired via DNA damage repair mechanism. Survival of damaged keratinocytes by increased anti-apoptotic signaling pathways or decreased pro-apoptotic signaling pathways will lead to clonal expansion of them during skin tumor promotion, which is followed by the formation of papilloma and then squamous cell carcinoma. In this chapter, we outline the functional significance of three – AKT, STAT3, and MAPK – anti-apoptotic signaling pathways and TC-PTP as a proapoptotic signaling pathway in the regulation of apoptosis during skin tumor initiation. Besides them, different signaling pathways are involved in modulating apoptosis during skin tumor initiation depending on the types of environmental assaults and interconnected with signaling pathways we mentioned in this chapter. Further understanding of signaling mechanisms and their function in environmentally induced epidermal apoptosis during tumor initiation will contribute to develop novel therapeutic interventions for the prevention and treatment of skin cancer.

#### **Acknowledgements**

This work was supported by the institutional fund from University of Texas Rio Grande Valley (to D.J. Kim) and the Ministry of Science, ICT and Future Planning (NRF-2020R1A2B5B02001804) (to Y.-Y. Cho).

*Regulation of Apoptosis during Environmental Skin Tumor Initiation DOI: http://dx.doi.org/10.5772/intechopen.97542*
