Cancer

Breast cancer

PDK1 is important in mediating migration and metastasis of breast cancer cells.
 

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +361, p<0.002); and Skin melanomas - malignant (%CFC= +85, p<0.001). The COSMIC website notes an up-regulated expression score for PDK1 in diverse human cancers of 439, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 166 for this protein kinase in human cancers was 2.8-fold of the average score of 60 for the human protein kinases.

Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis. Tyrosine phosphorylation induced by pervanadate in PDK1 can be partly reduced through a Y9F mutation in PDK1. Activation of PDK1 can be inhibited through a S241A mutation. PDK1 phosphotransferase activity can be reduced 3-fold with a A277V mutation. MELK-mediated phosphorylation can be inhibited through a T354A mutation. General phosphotransferase activity can also be reduced through either a Y373F, or a Y376F mutation. PDK1 phosphorylation of MAP3K5 can be ablated through the S394A and S398A mutations. Membrane localization via PDGF can be inhibited through a R474A mutation. Akt phosphorylation by PDK1 can be increased with a T513E mutation.

Percent mutation rates per 100 amino acids length in human cancers: 0.04 % in 25273 diverse cancer specimens. This rate is -46 % lower than the average rate of 0.075 % calculated for human protein kinases in general.

Highest percent mutation rates per 100 amino acids length in human cancers: 0.17 % in 1270 large intestine cancers tested; 0.16 % in 895 skin cancers tested; 0.14 % in 127 biliary tract cancers tested; 0.13 % in 273 cervix cancers tested; 0.09 % in 603 endometrium cancers tested; 0.08 % in 891 ovary cancers tested; 0.06 % in 589 stomach cancers tested; 0.06 % in 1768 lung cancers tested; 0.05 % in 710 oesophagus cancers tested; 0.05 % in 2082 central nervous system cancers tested; 0.04 % in 441 autonomic ganglia cancers tested; 0.04 % in 1490 breast cancers tested; 0.03 % in 548 urinary tract cancers tested; 0.02 % in 939 prostate cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 1512 liver cancers tested; 0.01 % in 1360 kidney cancers tested.

None > 3 in 20,713 cancer specimens

Only 1 deletion and 1 insertion, and no complex mutations are noted on the COSMIC website. About 39% of the point mutations are silent and do not change the amino acid sequence of the protein kinase.