Page 164 - D. Cancer biology

[D. Cancer biology-105]

NSMF promotes colorectal cancer growth via the protection

of replication stress

Kyeong Jin Shin¹, Yu Jin Lee¹, Hongtae Kim¹, Young Chan Chae¹

¹Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Korea

Deregulation of DNA damage response (DDR) and replication stress (RS) could lead to genomic instability. Early in
tumorigenesis, DDR and RS pathway serves a tumor-suppressive role, leading to checkpoint-imposed senescence
or apoptosis. On the other hand, in advanced tumor that overcome DDR barrier, this pathway may help the tumor

to cope with replication stress and thrive despite the enhanced genotoxic stress. Therefore, understanding how

cancer cells control this balance is important to discovering targets for treatment and prognosis as well as
understanding the pathogenesis and progression of cancer. In this study, we identified NSMF as a novel protein
that recognizes DNA damage. NSMF is highly expressed in several cancers, especially colorectal cancer, and is

related to poor prognosis in patients. The cancer cell growth was decreased when NSMF expression was inhibited,
caused by cell cycle arrest. In particular, NSMF-deficient cell became more sensitive to HU-induced replication stress.

Finally, we confirmed that the onset and growth of colorectal cancer was suppressed and the survival rate was
increased in NSMF KO mice compared with WT. Taken together, we found that NSMF could regulate the growth of

colorectal cancer through the regulation of replication stress.