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| Status |
Public on Jul 31, 2013 |
| Title |
PDK1 Signaling Towards PLK1-Myc Activation Confers Oncogenic Transformation and Tumor Initiating Cell Activation and Resistance to mTOR-targeted Therapy. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Although 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been predominately linked to PI3K-AKT pathway, it may also evoke additional signaling outputs to promote tumorigenesis. Here we report that PDK1 directly induces phosphorylation of Polo-like kinase 1 (PLK1), which in turn induces Myc phosphorylation and protein accumulation. We show that PDK1-PLK1-Myc signaling is critical for cancer cell growth and survival and small molecule inhibition of PDK1/PLK1 provides an effective approach for therapeutic targeting Myc-dependency. Intriguingly, PDK1-PLK1-Myc signaling induces an embryonic stem cell-like gene signature associated with aggressive tumor behaviors and is a robust signaling axis driving cancer stem cell (CSC) self renewal. Finally, we show that PLK1 inhibitor synergizes with mTOR inhibitor to induce synergistic anti-tumor effect in colorectal cancer by antagonizing a compensatory Myc induction. These findings identify a novel pathway in human cancer and CSC activation and provide a therapeutic strategy for targeting Myc-associated tumorigenesis and therapeutic resistance.
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| Overall design |
Gene expression profiling of Human Embryonic Kidney Cells (HEK-TERV) under different conditions: PMN, PDK1, MYC and E545K
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| Contributor(s) |
Tan J, Li Z, Lee PL, Guan P, Aau MY, Lee ST, Feng M, Lim CZ, Lee EY, Wee ZN, Lim YC, Karuturi RK, Yu Q |
| Citation(s) |
23887393 |
| Submission date |
Jul 14, 2011 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Peiyong Guan |
| E-mail(s) |
p.g@u.duke.nus.edu
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| Organization name |
Genome Institute of Singapore
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| Street address |
60 Biopolis Street, Genome, #02-01
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| City |
Singapore |
| ZIP/Postal code |
138672 |
| Country |
Singapore |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA144447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30669_HEK_Sample_Probe_Profile.txt.gz |
6.1 Mb |
(ftp)(http) |
TXT |
| GSE30669_PDK1_non-normalized.txt.gz |
2.2 Mb |
(ftp)(http) |
TXT |
| GSE30669_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
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