DDX53 Promotes Cancer Stem Cell-Like Properties and Autophagy.
Although cancer/testis antigen DDX53 confers anti-cancer drug-resistance, the effect of DDX53 on cancer stem cell-like properties and autophagy remains unknown. MDA-MB-231 (CD133+) cells showed higher expression of DDX53, SOX-2, NANOG and MDR1 than MDA-MB-231 (CD133-). DDX53 increasedin vitroself-renewal activity of MCF-7 while decreasing expression of DDX53 by siRNA loweredin vitroself-renewal activity of MDA-MB-231. DDX53 showed an interaction with EGFR and binding to the promoter sequences of EGFR. DDX53 induced resistance to anti-cancer drugs in MCF-7 cells while decreased expression of DDX53 by siRNA increased the sensitivity of MDA-MB-231 to anti-cancer drugs. Negative regulators of DDX53, such as miR-200b and miR-217, increased the sensitivity of MDA-MB-231 to anti-cancer drugs. MDA-MB-231 showed higher expression of autophagy marker proteins such as ATG-5, pBeclin1Ser15and LC-3I/II compared with MCF-7. DDX53 regulated the expression of marker proteins of autophagy in MCF-7 and MDA-MB-231 cells. miR-200b and miR-217 negatively regulated the expression of autophagy marker proteins. Chromatin immunoprecipitation assays showed the direct regulation of ATG-5. The decreased expression of ATG-5 by siRNA increased the sensitivity to anti-cancer drugs in MDA-MB-231 cells. In conclusion, DDX53 promotes stem cell-like properties, autophagy, and confers resistance to anti-cancer drugs in breast cancer cells.
Department of Biochemistry, Kangwon National University, Chunchon 24341, Korea.
Hyuna
H
Kim
Department of Biochemistry, Kangwon National University, Chunchon 24341, Korea.
Youngmi
Y
Kim
Department of Biochemistry, Kangwon National University, Chunchon 24341, Korea.
Dooil
D
Jeoung
D001343:Autophagy / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D014162:Transfection
C454199:DDX53 protein, human; D053487:DEAD-box RNA Helicases
DDX53; EGFR; anti-cancer drug-resistance; autophagy; stem cell-like properties