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Signals Controlling Un‐Differentiated States in Embryonic Stem and Cancer Cells: Role of the Phosphatidylinositol 3′ Kinase Pathway
Author(s) -
Voskas Daniel,
Ling Ling Sunny,
Woodgett James Robert
Publication year - 2014
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24603
Subject(s) - wnt signaling pathway , biology , pi3k/akt/mtor pathway , microbiology and biotechnology , signal transduction , stem cell , protein kinase b , hippo signaling pathway , pten , hes3 signaling axis , embryonic stem cell , cancer stem cell , cancer research , genetics , notch signaling pathway , gene
The capacity of embryonic stem (ES) cells to differentiate into cell lineages comprising the three germ layers makes them powerful tools for studying mammalian early embryonic development in vitro. The human body consists of approximately 210 different somatic cell types, the majority of which have limited proliferative capacity. However, both stem cells and cancer cells bypass this replicative barrier and undergo symmetric division indefinitely when cultured under defined conditions. Several signal transduction pathways play important roles in regulating stem cell development, and aberrant expression of components of these pathways is linked to cancer. Among signaling systems, the critical role of leukemia inhibitory factor (LIF) coupled to the Jak/STAT3 (signal transduction and activation of transcription‐3) pathway in maintaining stem cell self‐renewal has been extensively reviewed. This pathway additionally plays multiple roles in tumorigenesis. Likewise, the phosphatidylinositide 3‐kinase (PI3K)/protein kinase B (PKB/Akt) pathway has been determined to play an important role in both stem cell maintenance and tumor development. This pathway is often induced in cancer with frequent mutational activation of the catalytic subunit of PI3K or loss of a primary PI3K antagonist, phosphatase and tensin homolog deleted on chromosome ten (PTEN). This review focusses on roles of the PI3K signal transduction pathway components, with emphasis on functions in stem cell maintenance and cancer. Since the PI3K pathway impinges on and collaborates with other signaling pathways in regulating stem cell development and/or cancer, aspects of the canonical Wnt, Ras/mitogen‐activated protein kinase (MAPK), and TGF‐β signaling pathways are also discussed. J. Cell. Physiol. 229: 1312–1322, 2014. © 2014 The Authors. Published by Wiley Periodicals, Inc.