Abstract
TGFbetas are thought to have tumor suppressor activity in many organ systems, but receptor inactivation in mouse models has not previously resulted in increased spontaneous tumorigenesis. A study in this issue of Cancer Cell shows that mice with a targeted knockout of the type II TGFbeta receptor in stratified epithelia specifically develop spontaneous squamous cell carcinomas in the anogenital region, but not in the skin. Loss of TGFbeta signaling appears to destabilize the epithelium such that homeostasis fails in the face of persistent proliferative challenge, a normal feature of the anogenital site, and latent invasive and migratory phenotypes are unmasked.
MeSH terms
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Animals
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Anus Neoplasms / metabolism
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Anus Neoplasms / pathology
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Apoptosis*
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Carcinoma, Squamous Cell / enzymology
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Movement
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Cell Proliferation*
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Extracellular Matrix / metabolism
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Focal Adhesion Protein-Tyrosine Kinases / metabolism
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Homeostasis
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Humans
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Integrins / metabolism
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Keratin-14 / genetics
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Mice
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Mice, Knockout
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Mutation
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Neoplasm Invasiveness
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Papilloma / metabolism
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Papilloma / pathology
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Promoter Regions, Genetic
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Protein Serine-Threonine Kinases / deficiency
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Receptor, Transforming Growth Factor-beta Type II
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Receptors, Transforming Growth Factor beta / deficiency
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism*
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Signal Transduction*
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Skin / metabolism
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Skin / pathology
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Skin / physiopathology
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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Time Factors
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Transforming Growth Factor beta / metabolism*
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Urogenital Neoplasms / metabolism
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Urogenital Neoplasms / pathology
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Wound Healing
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ras Proteins / genetics
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ras Proteins / metabolism
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src-Family Kinases / metabolism
Substances
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Integrins
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KRT14 protein, human
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Keratin-14
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Focal Adhesion Protein-Tyrosine Kinases
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src-Family Kinases
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Protein Serine-Threonine Kinases
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Receptor, Transforming Growth Factor-beta Type II
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ras Proteins