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] |