Page 58 - D. Cancer biology

[D. Cancer biology-42]

Epigenetically transitional cancer cells show short-term

resistance and change into medium-term-resistant cells by

drug treatment

Shiv Poojan¹, Seung-Hyun Bae¹˙², Jae-Woong Min³˙⁴˙⁵, Eun Young Lee¹, Yura Song¹, Hee Yeon Kim¹, Hye
Won Sim¹, Eun-Kyung Kang¹, Young-Ho Kim¹, Hae-Ock Lee³˙⁴˙⁵, Yourae Hong³˙⁴˙⁵, Woong-Yang Park³˙⁴˙⁵,

Hyonchol Jang¹˙²˙*, Kyeong-Man Hong¹˙*

¹Research Institute, National Cancer Center, Goyang-si KS009, Korea, ²Department of Cancer Biomedical Science, National Cancer Center
Graduate School of Cancer Science and Policy, Goyang-si KS009, Korea, ³Samsung Genome Institute, Samsung Medical Center, Seoul KS013,

Korea, ⁴Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon KS002, Korea, ⁵Department of Health
Sciences and Technology, Sungkyunkwan University, Seoul KS013, Korea

Epigenetically reprogrammed cancer cells for H460 (R-H460) were established by transient introduction of

reprogramming factors. Then, the R-H460 cells were induced to differentiate by withdrawal of stem cell media for
various durations, which resulted in differentiated R-H460 (dR-H460). The dR-H460 cells with 13-day differentiation

(13dR-H460 cells) formed significantly larger number of drug-resistant colonies to both cisplatin and paclitaxel, in
contrast to the dR-H460 cells with 40 day differentiation (40dR-H460 cells), which lost their drug resistance; this

suggests that 13dR-cancer cells are short-term (less than a month)-resistant cells. The resistant phenotype of the
cisplatin-resistant (CR) colonies obtained from cisplatin treatment was maintained for 2-3 months after drug

treatment, suggesting that drug treatments make short-term-resistant cells into medium-term-resistant ones. In
single-cell analyses, heterogeneity did not increase in 13dR-H460, suggesting that short-term-resistant cancer cells

rather than heterogeneous cells may confer epigenetic-driven drug resistance in our reprogrammed cancer model.
The epigenetic-driven drug-resistant mechanisms could provide new cancer-fighting strategies entailing control of

cancer cells under epigenetic transition.