Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases

作者：Mancinelli Romina; Carpino Guido; Petrungaro Simonetta; Mammola Caterina Loredana; Tomaipitinca Luana; Filippini Antonio; Facchiano Antonio; Ziparo Elio; Giampietri Claudia

来源：Oxidative Medicine and Cellular Longevity, 2017, 2017: 4629495.

DOI：10.1155/2017/4629495

<jats:p>GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3<jats:italic>α</jats:italic> and GSK-3<jats:italic>β</jats:italic> isoforms, both active under basal conditions and inactivated upon phosphorylation by different upstream kinases. Initially discovered as a regulator of glycogen synthesis, GSK-3 is also involved in several signaling pathways controlling many different key functions. Here, we discuss recent advances regarding (i) GSK-3 structure, function, regulation, and involvement in several cancers, including hepatocarcinoma, cholangiocarcinoma, breast cancer, prostate cancer, leukemia, and melanoma (active GSK-3 has been shown to induce apoptosis in some cases or inhibit apoptosis in other cases and to induce cancer progression or inhibit tumor cell proliferation, suggesting that different GSK-3 modulators may address different specific targets); (ii) GSK-3 involvement in autophagy modulation, reviewing signaling pathways involved in neurodegenerative and liver diseases; (iii) GSK-3 role in oxidative stress and autophagic cell death, focusing on liver injury; (iv) GSK-3 as a possible therapeutic target of natural substances and synthetic inhibitors in many diseases; and (v) GSK-3 role as modulator of mammalian aging, related to metabolic alterations characterizing senescent cells and age-related diseases. Studies summarized here underline the GSK-3 multifaceted role and indicate such kinase as a molecular target in different pathologies, including diseases associated with autophagy dysregulation.</jats:p>

• 出版日期2017