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RNA binding protein RBM3 promotes a cancer stem cell phenotype with multidrug resistance
Author(s) -
Venugopal Anand,
Kwatra Deep,
Stecklein Shane,
Ramalingam Satish,
Subramaniam Dharmalingam,
Anant Shrikant
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1161.2
Subject(s) - downregulation and upregulation , doxorubicin , cancer research , angiogenesis , multiple drug resistance , stem cell , biology , cancer stem cell , chemistry , microbiology and biotechnology , drug resistance , gene , chemotherapy , genetics
RNA binding protein RBM3 functions to posttranscriptionally regulate mRNA by altering its stability and translation. We recently demonstrated that RBM3 acts as a proto‐oncogene that significantly increases cell proliferation, anchorage independent growth and angiogenesis. We have also observed that RBM3 overexpression in NIH3T3 cells promotes a stem‐like phenotype with upregulation of the putative quiescent stem cell marker DCLK1. Using a doxycycline (Dox) inducible system, we overexpressed RBM3 in the colorectal cancer cell line HCT116. RBM3 induction promoted spheroid formation compared to vector control. We also observed an increase in HES‐1 mRNA and protein indicating an increase in Notch activity. In addition, there was increased resistance to the antineoplastic agents doxorubicin and paclitaxel. Induction of RBM3 upregulated expression of multidrug resistance protein 2 (MRP2) and p‐glycoprotein (P‐gp), which correlated with a decrease in doxorubicin uptake and increase in doxorubicin efflux. This decrease in uptake could be partially rescued with the MRP inhibitor MK571. We conclude that RBM3 overexpression can promote a chemotherapy resistant stem‐like phenotype in colorectal cancer cells.