Melanoma Molecular Maps Projects



Title: GSK3-beta pathway
Legend: GSK3-beta is a cytoplasmic serine/threonine protein kinase that is known to play central roles in a variety of biological processes such as glucose metabolism, cell cycle, cell differentiation, cell migration and cell survival through a number of signaling pathways (e.g. Wnt/beta-catenin, Hedgehog, Notch, and insulin) [1]. Dysregulated hyperactivity of GSK3 is associated with various diseases and in vitro and in vivo studies have increasingly implicated that GSK3 inhibitors are promising therapeutics in diabetes mellitus, inflammation, psychiatric/neurodegenerative diseases, ischemia, and stem cell regeneration [2,3]. As regards tumor biology, the role of GSK3-beta is not univocal: in fact, by inhibiting the WNT/beta-catenin pathway, GSK3-beta can oppose cancerogenesis in colon carcinoma models, while opposite effects appear to occur in other models, including melanoma [4,5]. Consequently, GSK3 inhibitors are being developed to treat cancer as well [2,3]. REFERENCES: [1] . [2] Medina M, Curr Opin Drug Discov Devel 2008, 11:533-43. [3] Martinez A, Med Res Rev 2008, 28:773-96. [4] Wada A , Front Biosci 2009, 14:1558-70. [5] Luo J, Cancer Lett 2009, 273:194-200. CITED MOLECULES: AKT (protein kinase B, PKB), b-Catenin (beta catenin), Bcl-2 (B-cell CLL/lymphoma 2), Bcl-XL (BCL2-like 1, BCL2L1), BRAF (v-Raf murine sarcoma viral oncogene homolog B), c-FOS (v-Fos murine osteosarcoma viral oncogene homolog), c-JUN (v-Jun oncogene homolog), CKIe (casein kinase 1, epsilon, CSNK1E), c-MYC (v-Myc avian myelocytomatosis oncogene homolog), CRAF (v-Raf-1 murine leukemia viral oncogene homolog 1), Cyclin D, DSH (dishevelled), DW1/2 (drug), FRAT (frequently rearranged in advanced T-cell lymphomas), Frizzled (frizzled domain-containing receptor), Glycogen synthase, GPCR (G protein coupled receptor), GRB2 (growth factor receptor-bound protein 2), GSK3b (glycogen synthase kinase 3 beta), HDM2 (MDM2 p53 binding protein homolog, mouse double minute 2), IGF1 (insulin like growth factor 1), IGF1R (IGF1 receptor), IPP2 (protein phosphatase 1, regulatory [inhibitor] subunit 2, PPP1R2, protein phosphatase inhibitor 2), IRS1(insulin receptor substrate 1), Lithium (drug), LRP5 (low density lipoprotein receptor-related protein 5), MARK (microtubule affinity-regulating kinase 1), MAX (MYC associated factor X), mTOR (mammalian target of rapamycin), NFkB (nuclear factor kappa B), Noxa (PMAIP1, APR, BH3-only protein, pro-apoptotic), Nutlin-3 (drug), p21/CIP1 (Waf1), p53 (TP53 tumor suppressor), PDK1 (PIP3 dependent kinase 1), PI3K (phosphatidyl inositol 3-kinase), PIP2, PIP3 (phosphatidyl-inositol bis- tris-phosphate), PP1 (protein phosphatase 1), Proteasome, PTEN (phosphatase and tensin homolog), RAS (v-Ras oncogene homolog), RS6K (ribosomal protein S6 kinase), RTK (receptor tyrosine kinase), SHC (Src homology 2 domain containing protein), Sorafenib (drug), SOS (son of sevenless homolog), Survivin (baculoviral IAP repeat-containing 5, BIRC5), TCF/LEF (T cell-specific transcription factor, lymphoid enhancer-binding factor), TSC (tuberous sclerosis complex).
Author: The MMMP Team (updated: March 2009)

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