Akt Signaling Leads to Stem Cell Activation and Promotes Tumor Development in Epidermis. (17th June 2014)

• Record Type: Journal Article
• Authors: Segrelles, Carmen; García-Escudero, Ramón; Garín, Maria I.; Aranda, Juan F.; Hernández, Pilar; Ariza, José M.; Santos, Mirentxu; Paramio, Jesús M.; Lorz, Corina
• Is Part Of: Stem cells. Volume 32:Number 7(2014:Jul.)
• Page Start: 1917
• Page End: 1928
• Publication Date: 2014-06-17
• Subjects: Tissue-specific stem cells -- Cancer -- Epidermis -- Cancer stem cells; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1669
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : Hair follicle stem cells (HF-SCs) alternate between periods of quiescence and proliferation, to finally differentiate into all the cell types that constitute the hair follicle. Also, they have been recently identified as cells of origin in skin cancer. HF-SCs localize in a precise region of the hair follicle, the bulge, and molecular markers for this population have been established. Thus, HF-SCs are good model to study the potential role of oncogenic activations on SC physiology. Expression of a permanently active form of Akt (myrAkt) in basal cells leads to Akt hyperactivation specifically in the CD34 + Itga6 H population. This activation causes bulge stem cells to exit from quiescence increasing their response to proliferative stimuli and affecting some functions such as cell migration. HF-SC identity upon Akt activation is preserved; in this sense, increased proliferation does not result in stem cell exhaustion with age suggesting that Akt activation does not affect self-renewal an important aspect for normal tissue maintenance and cancer development. Genome-wide transcriptome analysis of HF-SC isolated from myrAkt and wild-type epidermis underscores changes in metabolic pathways characteristic of cancer cells. These differences manifest during a two-step carcinogenesis protocol in which Akt activation in HF-SCs results in increased tumor development and malignant transformation. Stem Cells 2014;32:1917–1928