A New Model for Raf Kinase Inhibitory Protein Induced Chemotherapeutic Resistance
- Publication Date
- January 18, 2012
- Journal
- PLOS ONE
- Authors
- Fahd Al Mulla, Milad S. Bitar, Jingwei Feng, Sungdae Park, et al
- Volume
- 7
- Issue
- 1
- Pages
- e29532
- DOI
- https://dx.plos.org/10.1371/journal.pone.0029532
- Publisher URL
- http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0029532
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/22279539
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261143
- Europe PMC
- http://europepmc.org/abstract/MED/22279539
- Web of Science
- 000299771900017
- Scopus
- 84862929922
- Mendeley
- http://www.mendeley.com/research/new-model-raf-kinase-inhibitory-protein-induced-chemotherapeutic-resistance
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Mendeley | Further Information
{"title"=>"A new model for Raf kinase inhibitory protein induced chemotherapeutic resistance", "type"=>"journal", "authors"=>[{"first_name"=>"Fahd", "last_name"=>"Al-Mulla", "scopus_author_id"=>"6603636413"}, {"first_name"=>"Milad S.", "last_name"=>"Bitar", "scopus_author_id"=>"7004051022"}, {"first_name"=>"Jingwei", "last_name"=>"Feng", "scopus_author_id"=>"55468608500"}, {"first_name"=>"Sungdae", "last_name"=>"Park", "scopus_author_id"=>"8443890000"}, {"first_name"=>"Kam C.", "last_name"=>"Yeung", "scopus_author_id"=>"7202425031"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84862929922", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84862929922", "pui"=>"364107264", "pmid"=>"22279539", "doi"=>"10.1371/journal.pone.0029532", "issn"=>"19326203"}, "id"=>"2a3ee252-61cb-3818-999f-5e18f4a825fd", "abstract"=>"Therapeutic resistance remains the most challenging aspect of treating cancer. Raf kinase inhibitory protein (RKIP) emerged as a molecule capable of sensitizing cancerous cells to radio- and chemotherapy. Moreover, this small evolutionary conserved molecule, endows significant resistance to cancer therapy when its expression is reduced or lost. RKIP has been shown to inhibit the Raf-MEK-ERK, NFκB, GRK and activate the GSK3β signaling pathways. Inhibition of Raf-MEK-ERK and NFκB remains the most prominent pathways implicated in the sensitization of cells to therapeutic drugs. Our purpose was to identify a possible link between RKIP-KEAP 1-NRF2 and drug resistance. To that end, RKIP-KEAP 1 association was tested in human colorectal cancer tissues using immunohistochemistry. RKIP miRNA silencing and its inducible overexpression were employed in HEK-293 immortalized cells, HT29 and HCT116 colon cancer cell lines to further investigate our aim. We show that RKIP enhanced Kelch-like ECH-associated protein1 (KEAP 1) stability in colorectal cancer tissues and HT29 CRC cell line. RKIP silencing in immortalized HEK-293 cells (termed HEK-499) correlated significantly with KEAP 1 protein degradation and subsequent NRF2 addiction in these cells. Moreover, RKIP depletion in HEK-499, compared to control cells, bestowed resistance to supra physiological levels of H(2)O(2) and Cisplatin possibly by upregulating NF-E2-related nuclear factor 2 (NRF2) responsive genes. Similarly, we observed a direct correlation between the extent of apoptosis, after treatment with Adriamycin, and the expression levels of RKIP/KEAP 1 in HT29 but not in HCT116 CRC cells. Our data illuminate, for the first time, the NRF2-KEAP 1 pathway as a possible target for personalized therapeutic intervention in RKIP depleted cancers.", "link"=>"http://www.mendeley.com/research/new-model-raf-kinase-inhibitory-protein-induced-chemotherapeutic-resistance", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>12, "Medicine and Dentistry"=>8, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Chemistry"=>1, "Computer Science"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>2, "Japan"=>1, "Poland"=>1, "France"=>1}, "group_count"=>1}CrossRef
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Europe PMC Database Citations | Further Information
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Relative Metric
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