Raf Kinase Inhibitory Protein: A Signal Transduction Modulator and Metastasis Suppressor

Author(s):  
Marsha Rich Rosner ◽  
Eva M. Eves
Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 306 ◽  
Author(s):  
Ali Yesilkanal ◽  
Marsha Rosner

Raf Kinase Inhibitory Protein (RKIP) is a highly conserved kinase inhibitor that functions as a metastasis suppressor in a variety of cancers. Since RKIP can reprogram tumor cells to a non-metastatic state by rewiring kinase networks, elucidating the mechanism by which RKIP acts not only reveals molecular mechanisms that regulate metastasis, but also represents an opportunity to target these signaling networks therapeutically. Although RKIP is often lost during metastatic progression, the mechanism by which this occurs in tumor cells is complex and not well understood. In this review, we summarize our current understanding of RKIP regulation in tumors and consider experimental and computational strategies for recovering or mimicking its function by targeting mediators of metastasis.


2015 ◽  
Author(s):  
Ali E. Yesilkanal ◽  
Casey Frankenberger ◽  
Daniel Rabe ◽  
Gary L. Johnson ◽  
Marsha R. Rosner

Oncotarget ◽  
2014 ◽  
Vol 5 (17) ◽  
pp. 7406-7419 ◽  
Author(s):  
Brianne Hill ◽  
Jason De Melo ◽  
Judy Yan ◽  
Anil Kapoor ◽  
Lizhi He ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 442 ◽  
Author(s):  
Ana Raquel-Cunha ◽  
Diana Cardoso-Carneiro ◽  
Rui M. Reis ◽  
Olga Martinho

Lung cancer is the most deadly neoplasm with the highest incidence in both genders, with non-small cell lung cancer (NSCLC) being the most frequent subtype. Somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are key drivers of NSCLC progression, with EGFR inhibitors being particularly beneficial for patients carrying the so-called “EGFR-sensitizing mutations”. However, patients eventually acquire resistance to these EGFR inhibitors, and a better knowledge of other driven and targetable proteins will allow the design of increasingly accurate drugs against patients’ specific molecular aberrations. Raf kinase inhibitory protein (RKIP) is an important modulator of relevant intracellular signaling pathways, including those controlled by EGFR, such as MAPK. It has been reported that it has metastasis suppressor activity and a prognostic role in several solid tumors, including lung cancer. In the present review, the potential use of RKIP in the clinic as a prognostic biomarker and predictor of therapy response in lung cancer is addressed.


2011 ◽  
Vol 7 (3) ◽  
pp. 928-941 ◽  
Author(s):  
Fahd al-Mulla ◽  
Milad S. Bitar ◽  
Zainab Taqi ◽  
Oliver Rath ◽  
Walter Kolch

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