Tumor antigen LRRC15 impedes adenoviral infection: implications for virus-based cancer therapy.
Adenoviruses for gene or oncolytic therapy are under development. Notable among these strategies is adenoviral delivery of the tumor suppressor p53. Since all therapeutics have limitations in certain settings, we have undertaken retroviral suppressor screens to identify genes conferring resistance to adenovirus-delivered p53. These studies identified the tumor antigen LRRC15, which is frequently overexpressed in multiple tumor types, as a repressor of cell death due to adenoviral p53. LRRC15, however, does not impede p53 function per se but impedes adenoviral infection. Specifically, LRRC15 causes redistribution of the coxsackievirus-adenovirus receptor away from the cell surface. This effect is manifested in less adenoviral binding to the surfaces of LRRC15-expressing cells. This discovery, therefore, not only is important for understanding adenoviral biology but also has potentially important implications for adenovirus-based anticancer therapeutics.
O'Prey
Jim
J
Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, United Kingdom.
Wilkinson
Simon
S
Ryan
Kevin M
KM
D000256:Adenoviridae / Q000235:genetics*; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D015316:Genetic Therapy; D005822:Genetic Vectors; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010957:Plasmids; D011991:Receptors, Virus; D014162:Transfection; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; C446297:LRRC15 protein, human; D008565:Membrane Proteins; D011991:Receptors, Virus; D016159:Tumor Suppressor Protein p53