Page 10 - D. Cancer biology

[D. Cancer biology-5]

Silencing of sirtuin 6 inhibits cell invasion and migration by

targeting matrix metalloproteinase-9 expression in human

breast cancer cells

On-Yu Hong¹, Hye-Yeon Jang¹, Hyun Jo Youn², Jong-Suk Kim¹˙*

¹Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju

54907, South Korea, ²Department of Surgery, Biomedical Research Institute of Jeonbuk National University
Hospital, Jeonju 54907, South Korea

Sirtuin6 (Sirt6), a member of the sirtuins protein family, plays various biological roles in cancer. Regulation of sirt6

is involved in tumor progression, including cancer cell adhesion, invasion and migration. Cancer invasion and
migration required for metastasis are the main causes of death in breast cancer patients. Matrix metalloproteinases

(MMPs) are crucial to regulate extracellular matrix (ECM) proteolysis. Especially gelatinases (MMP-9) has been closely
associated with metastasis. However, the studies on the role of SIRT6 in breast cancer metastasis is limited. In this

study, we investigated the effect of the inhibition of SIRT6 on protein kinase C (PKC) and cytokine mediated cancer
cell invasion and migration using MCF-7 and MDA-MDA-231 human breast cancer cell line. And, we also determined

the association of SIRT6 on MMP-9 expression. In conclusion, we demonstrated that the anti-invasive effects of the
SIRT6 on breast cancer cells might be through inhibiting the phosphorylation of MAPK and reducing AP-1 and NF-

kB DNA-binding activities, leading to downregulation of MMP-9 expression. Our results suggests the modulation
of SIRT6 as one of the therapeutic value for breast cancer metastasis by identifying SIRT6 in breast cancer cell

invasion and migration.