title: Expression of snail in epidermal keratinocytes promotes cutaneous inflammation and hyperplasia conducive to tumor formation.
abstract: Although metastasis is the most lethal consequence of tumor progression, comparatively little is known regarding the molecular machinery governing this process. In many carcinomas, there is a robust correlation between the expression of the transcription factor Snail and a poor prognosis, but the contribution of this protein to the metastatic process remains unresolved. Interestingly, the prolonged expression of Snail in epidermal keratinocytes is sufficient to recapitulate early features of metastasis. However, it does so without inducing a complete epithelial-mesenchymal transition (EMT), a developmental phenomenon mediated by Snail that is extensively invoked as the mechanism fueling tumorigenesis. Instead, we found that the local invasiveness of keratinocytes is the consequence of the recruitment and activity of macrophages. Moreover, keratinocyte proliferation is the product of an IL-17/IL-6/Stat3 signaling module initiated by activated resident γδT cells in the transgenic skin. Together, these phenotypes prime the transgenic skin for the formation and metastasis of tumors in response to chemically induced carcinogenesis. Thus, the contribution of Snail to the progression of carcinomas is largely through the creation of a hyperproliferative and inflammatory niche that facilitates tumor development and dissemination.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California San Diego, Natural Science Building Room 6113, 9500 Gilman Drive, MC 0380, La Jolla, CA 92093, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Du
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Tuan-Lin
authors.initials: TL
authors.lastname: Tan
authors.forename: Pedro
authors.initials: P
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Lee
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yu
authors.forename: Colin
authors.initials: C
authors.lastname: Jamora
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003872:Dermatitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020381:Interleukin-17; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D000071250:Snail Family Transcription Factors; C494087:Stat3 protein, mouse; D014157:Transcription Factors