Table 1

Paradoxical role of GSK3β in various human cancers

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]


Mishra Molecular Cancer 2010 9:144   doi:10.1186/1476-4598-9-144

Open Data