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Rak Functions as a Tumor Suppressor by Regulating PTEN Protein Stability and Function
Open accessAbstract
Summary Expression of PTEN tumor suppressor is frequently lost in breast cancer in the absence of mutation or promoter methylation through as yet undetermined mechanisms. In this study, we demonstrated that the Rak tyrosine kinase physically interacts with PTEN and phosphorylates PTEN on Tyr 336. The knockdown of Rak enhanced the binding of PTEN to its E3 ligase, NEDD4-1, and promoted PTEN polyubiquitination, leading to PTEN protein degradation. Notably, ectopic expression of Rak effectively suppressed breast cancer cell proliferation, invasion, and colony formation in vitro and tumor growth in vivo. Furthermore, Rak knockdown was sufficient to transform normal mammary epithelial cells. Therefore, Rak acts as a bona fide tumor suppressor gene through the mechanism of regulating PTEN protein stability and function.
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Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
Cited by
The functions and regulation of the PTEN tumour suppressor
Song, M. S., Salmena, L., & Pandolfi, P. P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3330 · Cited by 1,926
Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth
Zhang, L., Zhang, S., Yao, J., Lowery, F. J., Zhang, Q., Huang, W.-C., Li, P., Li, M., Wang, X., Zhang, C., et al. (2015) · Nature · doi:10.1038/nature15376 · Cited by 1,175
The functions and regulation of the PTEN tumour suppressor: new modes and prospects
Lee, Y.-R., Chen, M., & Pandolfi, P. P. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0015-0 · Cited by 917
Regulating tumor suppressor genes: post-translational modifications
Chen, L., Liu, S., & Tao, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0196-9 · Cited by 449
PTEN function: the long and the short of it
Hopkins, B. D., Hodakoski, C., Barrows, D., Mense, S. M., & Parsons, R. E. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.006 · Cited by 309
Metadata
- Authors
- Yim, E.-K., Peng, G., Dai, H., Hu, R., Li, K., Lu, Y., Mills, G. B., Meric-Bernstam, F., Hennessy, B. T., Craven, R. J., & Lin, S.-Y.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 15
- Issue
- 4
- Pages
- 304-314
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2062104023
- Cited by
- 209
- References
- 1
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yim, E.-K., Peng, G., Dai, H., Hu, R., Li, K., Lu, Y., Mills, G. B., Meric-Bernstam, F., Hennessy, B. T., Craven, R. J., & Lin, S.-Y. (2009). Rak Functions as a Tumor Suppressor by Regulating PTEN Protein Stability and Function. Cancer Cell. https://doi.org/10.1016/j.ccr.2009.02.012
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