Page 6 - D. Cancer biology

[D. Cancer biology-3]

Regulatory mechanism of MKK7 by METTL21B in gastric

cancer

Jae Gwang Park¹˙#, Long You²˙#, Yo Han Hong², Wooram Choi², Jieun Oh², Chaoran Song²,

Han Gyung Kim², Deok Jeong², Jae Youl Cho²

¹Colorectal Cancer Branch, National Cancer Center, Goyang 10408, Korea, ²Integrative biotechnology,
Sungkyunkwan University, Suwon 16419, Korea

Gastric cancer is the one of the most lethal diseases and third cause of cancer related mortality. Gastric cancer is
involved in various oncogenic signaling pathway. Mitogen-activated protein kinase pathway is a major cell-mediated

cascade that regulates processes that regulate tumorigenic responses. Methylation as one of the post-translational
modifications affects various physiological processes. METTL21B is a non-histone protein lysine methyltransferase.

The recently discovered METTL21B has reported little of its function and methylated substrates. According to
microarray analysis against Asian Cancer Research Group, METTL21B was significantly down-regulated in tumor

compared to normal. METTL21B was almost occurred genetic alteration in methyltransferase domain. METTL21B
expression was inhibited in most gastric tumor tissue and cancer cell lines. And then, METTL21B interacted and

methylated MKK7 at lysine 296. METTL21B mediated methylation of MKK7 regulated MAPK signaling pathway.
Moreover, METTL21B affected tumor metastasis including invasion, migration and colony formation in vitro and in

vivo model. Taken together, methylation of METTL21B-mediated MKK7 stimulates the MAPK signaling pathway and
regulates gastric cancer metastasis leading to tumorigenesis.