Brain cancers frequently recur or progress as focal masses
after treatment with ionizing radiation. Radiation used to target
gliomas may expand the cancer stem cell population and enhance the aggressiveness of
tumors; however, the mechanisms underlying the expansion of cancer stem cell population after radiation have remained unclear. In this study, we show that LCK (lymphocyte-specific
protein tyrosine kinase) is involved in the fractionated radiation-induced expansion of the
glioma-initiating cell population and acquisition of resistance to anticancer treatments. Fractionated radiation caused a selective increase in the activity of LCK, a Src family non-
receptor tyrosine kinase. The activities of other
Src family kinases Src, Fyn, and Lyn were not significantly increased. Moreover, knockdown of LCK expression with a specific
small interfering RNA (
siRNA) effectively blocked fractionated radiation-induced expansion of the CD133(+) cell population.
siRNA targeting of LCK also suppressed fractionated radiation-induced expression of the
glioma stem cell marker
proteins CD133,
Nestin, and Musashi. Expression of the known self-renewal-related
proteins Notch2 and Sox2 in
glioma cells treated with fractionated radiation was also downregulated by LCK inhibition. Moreover,
siRNA-mediated knockdown of LCK effectively restored the sensitivity of
glioma cells to
cisplatin and
etoposide. These results indicate that the non-
receptor tyrosine kinase LCK is critically involved in fractionated radiation-induced expansion of the
glioma-initiating cell population and decreased cellular sensitivity to anticancer treatments. These findings may provide pivotal insights in the context of fractionated radiation-based therapeutic interventions in
brain cancer.