| Summary: | Autophagy is a ubiquitous degradation mechanism, which plays a critical role in cellular homeostasis. To test whether autophagy suppresses or supports the growth of tumors in the epidermis of the skin, we inactivated the essential autophagy gene <i>Atg7</i> specifically in the epidermal keratinocytes of mice (<i>Atg7<sup>∆ep</sup></i>) and subjected such mutant mice and fully autophagy-competent mice to tumorigenesis. The lack of epithelial Atg7 did not prevent tumor formation in response to 7, 12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O tetradecanoylphorbol-13-acetate (TPA) as the promoter of tumor growth. However, the number of tumors per mouse was reduced in mice with epithelial Atg7 deficiency. In the <i>K5-SOS EGFR<sup>wa2/wa2</sup></i> mouse model, epithelial tumors were initiated by Son of sevenless (SOS) in response to wounding. Within 12 weeks after tumor initiation, 60% of the autophagy-competent <i>K5-SOS EGFR<sup>wa2/wa2</sup></i> mice had tumors of 1 cm diameter and had to be sacrificed, whereas none of the <i>Atg7<sup>∆ep</sup> K5-SOS EGFR<sup>wa2/wa2</sup></i> mice formed tumors of this size. In summary, the deletion of <i>Atg7</i> reduced the growth of epithelial tumors in these two mouse models of skin cancer. Thus, our data show that the inhibition of autophagy limits the growth of epithelial skin tumors.
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