Targeting PDK1 in cancer
MetadataShow full item record
Abnormal activation of phosphoinositide 3-kinase (PI3K) signalling is very common in cancer, leading to deregulation of several intracellular processes normally controlled by this enzyme, including cell survival, growth, proliferation and migration. Mutations in the gene encoding the tumour suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which leads to uncontrolled activation of the PI3K pathway, are reported in different cancers. Among the downstream effectors of PI3Ks, 3-phosphoinositide- dependent protein kinase 1 (PDK1) and protein kinase B (PKB)/Akt have a key role in several cancer types. More recent data indicate that alteration of PDK1 is a critical component of oncogenic PI3K signalling in breast cancer, suggesting that inhibition of PDK1 can inhibit breast cancer progression. PDK1 has an essential role in regulating cell migration especially in the context of PTEN deficiency. Downregulation of PDK1 levels inhibits migration and experimental metastasis of human breast cancer cells. PDK1 activates a large number of proteins, including Akt, some PKC isoforms, S6K and SGK. Data also reveal that PDK1 is oncogenic and this is dependent on PI3K pathway. Therefore, accumulating evidence demonstrates that PDK1 is a valid therapeutic target and suggests that PDK1 inhibitors may be useful to prevent cancer progression and abnormal tissue dissemination. This review will focus on published data on the role of PDK1 in cancer and approaches used to inhibit PDK1. © 2011 Bentham Science Publishers Ltd.
Showing items related by title, author, creator and subject.
Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4Manu, K.; Shanmugam, M.; Rajendran, P.; Li, F.; Ramachandran, L.; Hay, H.; Kannaiyan, R.; Swamy, S.; Vali, S.; Kapoor, S.; Ramesh, B.; Bist, P.; Koay, E.; Lim, L.; Ahn, K.; Kumar, Alan Prem; Sethi, G. (2011)Background: Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related ...
Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate modelShanmugam, M.; Manu, K.; Ong, T.; Ramachandran, L.; Surana, R.; Bist, P.; Lim, L.; Kumar, Alan Prem; Hui, K.; Sethi, G. (2011)Increasing evidences indicate that CXCR4/CXCL12 signaling pathway plays a pivotal role in the process of distant site metastasis that accounts for more than 90% of prostate cancer related deaths in patients. Thus, novel ...
3-phosphoinositide-dependent protein kinase-1 as an emerging target in the management of breast cancerFyffe, C.; Falasca, Marco (2013)It should be noted that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a protein encoded by the PDPK1 gene, which plays a key role in the signaling pathways activated by several growth factors and hormones. PDK1 ...