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Table 1 Paradoxical role of GSK3β in various human cancers

From: Glycogen synthase kinase 3 beta: can it be a target for oral cancer

Cancer Types

Explanation for Tumour Suppressor Role of GSK3β

Skin cancer

(Cutaneous SCC)

Inactivation of GSK3β (higher pSer9GSK3β expression) [72]

Inactivation of GSK3β (lower pTyr216GSK3β expression) [60, 168]

Pharmacological inhibition of GSK3β in normal epithelial causes epithelial mesenchymal transition (EMT) and invasion [39]

Oral cancer

(OSCC)

Inactivation of GSK3β (higher pSer9GSK3β expression) [88]

The basal inactivated GSK3β (pSer9GSK3β) level in OSCC cell line is high [61–63]

Activation of GSK3β, can reverse EMT [64]

Larynx cancer

Inactivation of GSK3β (higher pSer9GSK3β expression) [88]

Esophageal cancer

Inactivation of GSK3β (higher pSer9GSK3β expression) [88]

Breast cancer

Overexpression of inactive GSK3β promotes [169], and active GSK3β suppress mammary tumours [168]

Active GSK3 increases chemosensitivity, cell cycle arrest and reduces mammary tumorigenecity [170–172]

Pharmacological inhibition of GSK3 in breast epithelial causes EMT and invasion [39]

Salivary gland cancer

Inactivation of GSK3β (pSer9GSK3β) observed in this tumor [88]

Nasopharyngeal cancer (SCC)

Inactivation of GSK3β observed and positively correlated with its upstream inactivating kinase Akt [173]

Lung cancer (SCC)

Inactivation of GSK3β reported [40]

Adenocarcinoma of Lung

Higher level of inactivated of GSK3β (pSer9GSK3β) observed [174]

Melanoma cancer

Inactivation of GSK3β reported [60]

Skin cancer (Basal cell carcinoma)

Inactivation of GSK3β reported [60]

Cancer Types

Explanation for Tumour Promoter Role of GSK3β

Pancreatic cancer

Pharmacological inhibition of GSK3 attenuates survival, proliferation and induce apoptosis [162, 163, 175]

Active GSK3β promotes growth [176]

Absence of inactive GSK3β (lower pSer9GSK3β expression) in tumors [88]

High level expression and nuclear accumulation association with kinase activity and tumor dedifferentiation [161, 177, 178]

Colorectal cancer

Pharmacological inhibition activates cell cycle arrest and induce apoptosis [158, 159, 175]

Absence of inactive GSK3β (lower pSer9GSK3β) in majority of tumors [88]

Increased expression/active GSK3β in these tumors [88, 159]

Myeloma cancer

GSK3β promotes growth and use of pharmacological inhibitor promotes apoptosis [83]

Hepatic cancer

Absence of inactive form of GSK3β (pSer9GSK3β) in these tumors [88]

Increase and active GSK3β expression [175]

Leukemia cancer

GSK3 activation enhances proliferation and survival [160, 179–181]

Missplicing at the kinase domain causing active GSK3β [179]

Stomach cancer

Absence of inactive GSK3β (pSer9GSK3β) in these tumours [88]

Active GSK3β observed frequently and its pharmacological inhibition attenuates survival, proliferation and induce apoptosis [175]

Ovarian cancer

GSK3β expression increases and it promotes cell division [156]

Prostate cancer

GSK3 activity favors replication of DNA and S-phase progression [157]

Thyroid cancer

Inhibition of GSK3 activity leads to growth suppression [182]

Gastro-Intestinal cancer

Higher and active GSK3β expression observed [166]

Absence of inactive GSK3β (pSer9GSK3β) in these tumors [88]

Renal cell carcinoma

Activation of GSK3β observed in this tumor [175]

Nuclear accumulation of GSK3β and its pharmacological inhibition suppress growth [178]

Glioma cancer

Pharmacological inhibition of GSK3 induces cell death [183]