Invited review article| Volume 50, ISSUE 1, P1-14, April 2008

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Impact of Stat3 activation upon skin biology: A dichotomy of its role between homeostasis and diseases


      Signal transducer and activator of transcription 3 (Stat3) is a latent cytoplasmic protein that conveys signals to the nucleus upon stimulation with IL-6, EGF, and many other cytokines/growth factors, leading to transcriptional activation of the downstream genes. It has been well defined that Stat3 plays critical roles in biological activities including cell proliferation, migration, survival, and oncogenesis. The in vivo role for Stat3 in the skin was elucidated using keratinocyte-specific Stat3 gene knockout mice, referred to as Stat3-disrutped mice. It was shown that Stat3 activation contributed to skin wound healing, keratinocyte migration, hair follicle growth, and resistance to UV irradiation-induced apoptosis. Furthermore, in the two-stage chemical carcinogenesis protocol, Stat3-disrupted mice did not develop any skin tumors. In contrast, transgenic mice with a constitutive active form of Stat3 (K5.Stat3C mice) developed squamous cell carcinoma (SCC) with a shorter latency and in much greater number compared to control mice. These results suggested a role for Stat3 not only in early stages of skin carcinogenesis but also in driving malignant progression in vivo. Moreover, Stat3 was consistently activated in epidermal keratinocytes in human psoriatic lesions, which has been assumed to recapitulate a condition of persistent wound healing reaction. Accordingly, K5.Stat3C mice were found to be psoriasis-prone. Finally, it was demonstrated that an inhibition of Stat3 activation ameliorated these pathological conditions, i.e., skin carcinogenesis and psoriasis. Here we will review the dichotomous roles for Stat3 in maintaining skin homeostasis and in the development of skin diseases such as psoriasis and skin cancer.


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      Shigetoshi Sano graduated and received his MD from Ehime University School of Medicine in 1983. He received his PhD degree from Osaka University School of Medicine in 1988. He worked in the Department of Microbiology and Immunology at Albert Einstein Medical College (in Dr. Barry R. Bloom's lab) as a research fellow from 1988 to 1992. He worked at the Department of Dermatology, Sakai Municipal Hospital from 1992 to 1994. He was subsequently promoted to assistant professor at the Department of Dermatology, Osaka University Graduate School of Medicine in 1992. From 2003 to 2004, he was a visiting associate professor at the Department of Carcinogenesis, University of Texas, USA. There he worked at the MD Anderson Cancer Center (in Dr. J. DiGiovanni's lab). From 2004 to 2005, he was head of the Department of Dermatology, Sumitomo Hospital, Osaka. He returned again to Department of Dermatology, Osaka University School of Medicine in 2005, and became an associate professor in 2006. Since 2007, he has been professor at the Department of Dermatology, Kochi Medical School. He won the Minami Prize in 2000, Galderma Prize in 2001, Eugene Farber Prize in 2005, and JSID Prize in 2006.