Exploring Rak tyrosine kinase function in breast cancer.
Protein tyrosine kinases have been implicated in the regulation of many cellular events such as cellular proliferation, differentiation and development. Deregulation of protein tyrosine kinase activity has been shown to result in human cancer. The majority of the protein tyrosine kinases studied to date localize to the cell membrane, where they function as components of signal transduction pathways. However, small group of nuclear tyrosine kinases has been identified that includes Rak. Our recent investigations demonstrated that Rak functions as a potent tumor suppressor by regulating PTEN protein stability and function. Rak also effectively suppresses phenotypes associated with in vitro transformation in breast cancer cells and tumorigenicity in vivo. Moreover, depletion of Rak is sufficient to induce tumorigenicity in mammary epithelial cells. However, the mechanisms by which Rak and its substrates function in cancer remain largely unexplored, leaving many potential therapeutic targets yet undiscovered. Therefore, fully elucidating the biological functions of Rak may contribute to effective therapeutic approaches for Rak-defective cancers.
Yim
Eun-Kyoung
EK
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Siwko
Stefan
S
Lin
Shiaw-Yih
SY
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*
D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D011505:Protein-Tyrosine Kinases; C092830:FRK protein, human; D018844:Cyclin-Dependent Kinases; D051059:PTEN Phosphohydrolase