title: Keratoacanthoma of the Lip: Activation of the mTOR Pathway, Tumor Suppressor Proteins, and Tumor Senescence.
abstract: The PI3K-PTEN-mTOR is one of the most important pathways involved in cancer development and progression; however, its role in keratoacanthoma (KA) is poorly understood. In this study, we investigated the activation of key proteins in the PI3K-mTOR pathway in lip KA. We analyzed the activation of the PI3K-PTEN-mTOR pathway using human tumor samples stained for well-established protein markers in this pathway, including pS6 and pAKT phosphoproteins. We assessed proliferation using Ki-67 and performed additional morphological and immunohistochemical analysis using anti-PTEN and anti-p16 antibodies.We found that the majority of KA labeled to pS6 and not pAKT. PTEN expression was inversely correlated with Ki-67 expression. In addition to PTEN expression, KA cells were positive for p16 senescence marker. PI3K-PTEN-mTOR pathway is activated in lip KA, leading to downstream activation of mTORC1, but not mTORC2. This pathway plays an important role in KA progression by promoting proliferation and activation of oncogenic-induced senescence.
authors.affiliation: From the Department of Periodontics and Oral Medicine, Laboratory of Epithelial Biology, University of Michigan School of Dentistry, Ann Arbor, MI (CSD, MDM, RMC, CHS); Department of Oral Pathology, School of Dentistry (CSD, MDM); and Department of Pathology, Hospital de Clínicas de Porto Alegre and Medical School, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil (LM).
authors.forename: Caroline Siviero
authors.initials: CS
authors.lastname: Dillenburg
authors.forename: Manoela Domingues
authors.initials: MD
authors.lastname: Martins
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Rogerio Moraes
authors.initials: RM
authors.lastname: Castilho
authors.forename: Cristiane Helena
authors.initials: CH
authors.lastname: Squarize
mesh_terms: D000368:Aged; D016922:Cellular Senescence / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007636:Keratoacanthoma / Q000378:metabolism / Q000473:pathology; D008048:Lip Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human