The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
AKT-Independent Signaling Downstream of Oncogenic PIK3CA Mutations in Human Cancer
Open accessAbstract
Summary Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs commonly in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phospho-protein profiling and functional genomic studies that many PIK3CA-mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation, and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization, and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA-mutant cancer cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations.
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Cites
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915
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Cited by
AKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
The emerging mechanisms of isoform-specific PI3K signalling
Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2882 · Cited by 1,767
Proteogenomics connects somatic mutations to signalling in breast cancer
CPTAC, N., Mertins, P., Mani, D. R., Ruggles, K. V., Gillette, M. A., Clauser, K. R., Wang, P., Wang, X., Qiao, J. W., Cao, S., et al. (2016) · Nature · doi:10.1038/nature18003 · Cited by 1,676
The nuts and bolts of AGC protein kinases
Pearce, L. R., Komander, D., & Alessi, D. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2822 · Cited by 1,294
Metadata
- Authors
- Vasudevan, K. M., Barbie, D. A., Davies, M. A., Rabinovsky, R., McNear, C. J., Kim, J. J., Hennessy, B. T., Tseng, H., Pochanard, P., Kim, S. Y., Dunn, I. F., Schinzel, A. C., Sandy, P., Hoersch, S., Sheng, Q., Gupta, P. B., Boehm, J. S., Reiling, J. H., Silver, S., Lu, Y., Stemke-Hale, K., Dutta, B., Joy, C., Sahin, A. A., Gonzalez-Angulo, A. M., Lluch, A., Rameh, L. E., Jacks, T., Root, D. E., Lander, E. S., Mills, G. B., Hahn, W. C., Sellers, W. R., & Garraway, L. A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 16
- Issue
- 1
- Pages
- 21-32
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1588880778
- Cited by
- 524
- References
- 5
- FWCI
- 17.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
