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Review
. 2017:2017:4629495.
doi: 10.1155/2017/4629495. Epub 2017 Dec 12.

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

Romina Mancinelli  1 , Guido Carpino  2 , Simonetta Petrungaro  1 , Caterina Loredana Mammola  1 , Luana Tomaipitinca  1 , Antonio Filippini  1 , Antonio Facchiano  3 , Elio Ziparo  1 , Claudia Giampietri  1
Affiliations
Review

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

Romina Mancinelli et al. Oxid Med Cell Longev. 2017.

Abstract

GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3α and GSK-3β 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.

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Figures

Figure 1
Figure 1
GSK-3 regulation.
Figure 2
Figure 2
Signaling pathways leading to GSK-3 inactivation.
Figure 3
Figure 3
Opposite role of GSK-3 in cancer.
Figure 4
Figure 4
Models of GSK-3 involvement in autophagy.
See this image and copyright information in PMC

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