Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer
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...
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MDPI AG
2022-11-01
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| author | Caterina Barresi Heidemarie Rossiter Maria Buchberger Johannes Pammer Supawadee Sukseree Maria Sibilia Erwin Tschachler Leopold Eckhart |
| author_facet | Caterina Barresi Heidemarie Rossiter Maria Buchberger Johannes Pammer Supawadee Sukseree Maria Sibilia Erwin Tschachler Leopold Eckhart |
| author_sort | Caterina Barresi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T18:24:37Z |
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| language | English |
| last_indexed | 2024-03-09T18:24:37Z |
| publishDate | 2022-11-01 |
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| series | Cells |
| spelling | doaj.art-8dafe93792c34854ab5c620f0e9256362023-11-24T07:59:28ZengMDPI AGCells2073-44092022-11-011122369110.3390/cells11223691Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin CancerCaterina Barresi0Heidemarie Rossiter1Maria Buchberger2Johannes Pammer3Supawadee Sukseree4Maria Sibilia5Erwin Tschachler6Leopold Eckhart7Department of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaClinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaCenter for Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Dermatology, Medical University of Vienna, 1090 Vienna, AustriaAutophagy 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.https://www.mdpi.com/2073-4409/11/22/3691autophagykeratinocytescarcinogenesistumorsquamous cell carcinomaepidermis |
| spellingShingle | Caterina Barresi Heidemarie Rossiter Maria Buchberger Johannes Pammer Supawadee Sukseree Maria Sibilia Erwin Tschachler Leopold Eckhart Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer Cells autophagy keratinocytes carcinogenesis tumor squamous cell carcinoma epidermis |
| title | Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer |
| title_full | Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer |
| title_fullStr | Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer |
| title_full_unstemmed | Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer |
| title_short | Inactivation of Autophagy in Keratinocytes Reduces Tumor Growth in Mouse Models of Epithelial Skin Cancer |
| title_sort | inactivation of autophagy in keratinocytes reduces tumor growth in mouse models of epithelial skin cancer |
| topic | autophagy keratinocytes carcinogenesis tumor squamous cell carcinoma epidermis |
| url | https://www.mdpi.com/2073-4409/11/22/3691 |
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